In Chapter 1, we will study the mesoporous silica nanoparticles (MSNs) based nanomaterials to overcome MDR through chemo-photodynamic therapy, which leads to an alteration in the ROS generation. Excessive ROS causes changes in the tumor microenvironment (TME) to combat cancer. The different possible approaches are explained at TME through enhanced ROS levels with recent examples. In the earlier sections, we were briefly explained cancer and its history. Later on sections, we focused on mesoporous silica (MSNs) synthesis techniques and their application toward overcoming multidrug resistance (MDR) cancers. The physicochemical characteristic features of MSNs, such as size, surface charge, and surface modifications, and their influence the activity towards cancers and MDR cancers. Next, functional modifications and therapeutic drugs loaded MSNs cellular internalization mechanisms, stimuli-responsive payload-releasing studies (internal or external stimuli). Furthermore, give possible explanations for ROS science, chemotherapy applications in ROS generation mechanism, and their applications to overcome MDR cancers. Next, Photodynamic therapy (PDT) basic principle of ROS generation, MSN's based PDT applications to overcome MDR cancers. Finally, we concluded that combination therapies chemodynamic and photodynamic studies of MSNs based studies were explained in detail.

In Chapter 2, we will go to explaining the ROS enrichment strategy by MSNs co- delivery of cisplatin (CP) and curcumin (Cur) to overcome MDR cancers through synergistic chemo-photodynamic therapy. In this theory, well-engineered MSNs were fabricated with Cur and CP to check their potency on MES-SA/DX5 DOX resistance cancer cells. The Pluronic-F127 polymer acts as a P-gp efflux inhibitor, and Cur used P-gp sensitizers. The Cur and CP were employed as photosensitizers and chemotherapeutic agents to the enhancement of ROS levels to overcome MDR cancer through a synergistic effect. The synthesized IBN-1-Cur nanoparticles and successive modifications are analyzed through physical and chemical analysis techniques, such as Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and dynamic light scattering (DLS) methods. Furthermore, surface-modified functional groups are analyzed to detect the primary amine functional groups by the traditional ninhydrin test. The ninhydrin test was employed to give possible explanations of amine modifications, further amine functional groups converted to acid functional groups in the presence of gutlatric-anhydrous. The Uv-visible based spectroscopic studies were employed to quantify the drug loading and release amount of CP. Next, Cur photostability studies and aqueous stability studies examined cur is used as a photosensitizer (PS). The Cur inside MSN's nanoparticle shows high stability compared with bare Cur, which means shell MSNs protected Cur species from light

and aqueous substances. Fluorescence microscopy studies have examined the cellular internalization of IBN-1-Cur-CP nanoparticles by taking advantage of Cur's self- fluorescence property. MTT assay was employed to study the in vitro anticancer-killing efficacy and DCFDA assay used to detect the reactive oxygen species (ROS) generation capacity by flow cytometry/fluorescence microscopic studies. ROS impacted mitochondrial membrane potential (MMP) is checking through JC-1 assay. Collectively, all physical-chemical studies and in vitro cell-based studies shows well-engineered size-controlled nanoparticle having good biocompatibility and overcome MDR through synergistic chemo-photodynamic therapy.
In chapter 3, core-shell Ag@MSNs are synthesized and analyzed by physicochemical techniques, such as FTIR, TEM, DLS, and thermogravimetric analysis (TGA) to a better understanding of the core-shell formation and doxorubicin (DOX) loading. Further, di-amine silane modifications are detected through ninhydrin test and electron spin resonance (ESR) studies employed to examine the copper signal in copper and DOX-loaded samples. DOX releasing studies conducted in different pH having physiological buffer solution (pH-5.0 and 7.4) detected by UV-visible spectroscopic studies. The Ag+ ion generation is estimated in hydrogen peroxide (H2O2) having different concentrations and pH values from Ag@MSNs, and consumption assay carried in cell culture medium to evaluate the Ag+ consumption rate.

Furthermore, in vitro cell viability studies were conducted against MES-SA/DX5 cells to check the potency of various nanoformulations by MTT assay. The AgNP is used as P-gp efflux inhibitors. Next, nanoparticle cell uptake studies detected using fluorescence microscopy studies by FITC-labeled Ag@MSNs. ROS generation efficacy was determined using DCFDA assay and lipid peroxidation assay performed to detect the degree of lipid peroxidation capacity after being exposed to different concentrations of nanoparticles. Our study findings eradicate MDR cancer through synergistic chemo-dynamic and metal ion therapy.

Chapter-1
1.0. History of cancer 25
1.1. Definition of cancer and treatment 25
1.2. Multidrug resistance (MDR) 27
2.0. MSNs synthesis and applications 29
2.1. MSNs Synthesis 30
2.2. MSNs Biocompatibility
3.0. MSNs based cancer drug delivery 33
3.1. MSNs intracellular uptake studies 34
3.1.1. MSNs trafficking inside cancer cells 35
4.0. MSNs used as stimuli-responsive drug delivery 35
4.1. pH-sensitive linker-modified MSNs 36
4.2. Light-activated drug delivery from MSNs 36
5.0. ROS Science 37
5.1. Significance of ROS 37
5.2. MSNs based ROS generation and significance 40
5.3. MSNs-photodynamic therapy (PDT) 40
5.3.1. PDT-basic principle and mechanism of action 40
5.3.2. Synergistic chemo-photo dynamic therapy of MSNs 43
6.0 References 44

Chapter-2
Overcome the Multi-Drug Resistance (MDR) Cancer through Synergistic Chemo-photodynamic Therapy by MSNs.
Abstract 65
2.0 . Introduction 66
2.1.0. Materials and methods 69
2.1.1. Materials 69
2.1.2. Characterization 70
2.1.3. Facile one-pot synthesis of Cue embedded IBN-1-Cur 70
2.1.4. Synthesis of amine-modified IBN-1-Cur by post-modification 71
2.1.5. Synthesis of acid-modified nanoparticle 71
2.1.6. Co-ordination of CP onto IBN-1-Cur-GA nanoparticle 72
2.1.7. CP kinetic delivery profile 72
2.1.8. Ninhydrin test 73
2.1.9. Cur Photo-stability assay 74
2.1.10. Detection of singlet oxygen (1O2) generation by DPBF assay 74
2.1.11. Cell culture 75
2.1.12. In vitro Cytotoxicity of IBN-1-Cur-CP and drug delivery into cells 75
2.1.13. Trypan blue assay 76
2.1.14. DCFDA assay 76
2.2. Results and discussion 78
2.2.1. Synthesis and characterization 78
2.2.2. Photo-bleaching studies 82
2.2.3. CP-drug releasing profile 85
2.2.4. In vitro singlet oxygen generation assay 87
2.2.5. In vitro cell viability assay 88
2.2.6. Trypan blue assay 89
2.2.7. In vitro cell uptake studies 90
2.2.8. DCFDA assay 91
2.3. Conclusion 92
2.4. References 92

Chapter 3
Silver Embedded Mesoporous Silica (Ag@MSNs) Core-shell Loaded Doxorubicin (DOX) via pH-Sensitive Delivery to Combat the DOX Resistance Cells of MES-SA/DX5 through Synergistic Metal ion-chemo Dynamic Therapy.
Abstract 104
3.0 . Introduction 106
3.1 Experimental section 110
3.1.1. Materials 110
3.1.2. The core-shell Ag@MSNs synthesis 110
3.1.3. Surfactant extraction 111
3.1.4. Di-amine modification onto Ag@MSNs 111
3.1.5. Copper chelation onto Ag@MSNs@NH-NH2 112
3.1.6. DOX loading 112
3.1.7. In vitro drug-releasing assay 113
3.1.8. Cell culture 113
3.1.9. In vitro cytotoxicity assessment assay 113
3.1.10. In vitro ROS measurement assay 114
3.2. Results and discussion 114
3.2.1. Physicochemical characterization 115
3.2.2. DOX loading 123
3.2.3. In vitro DOX releasing kinetics 125
3.2.4. In vitro H2O2 effect on Ag@MSNs 126
3.2.5. In vitro silver-releasing 128
3.2.6. Cellular uptake studies 132
3.2.7. Anti-cancer activity 133
3.3. Conclusion 137
3.4. References 138

Chapter-1
1. Faguet, G. B., A brief history of cancer: Age-old milestones underlying our current knowledge database. International Journal of Cancer 2015, 136, 2022–2036.
2. Maman, S.; Witz, I. P., A history of exploring cancer in context. Nature Reviews Cancer 2018, 18, 359–376.
3. DeVita, V. T.; Chu, E., A History of Cancer Chemotherapy. Cancer Research 2008, 68, 8643.
4. World Health, O., WHO report on cancer: setting priorities, investing wisely, and providing care for all. World Health Organization: Geneva, 2020.
5. Housman, G.; Byler, S.; Heerboth, S.; Lapinska, K.; Longacre, M.; Snyder, N.; Sarkar, S., Drug Resistance in Cancer: An Overview. Cancers 2014, 6, 1769–1792.
6. Farber, S.; Diamond, L. K.; Mercer, R. D.; Sylvester, R. F. Wolff, J. A., Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4- Aminopteroyl-Glutamic Acid (Aminopterin). New England Journal of Medicine 1948, 238, 787–793.
7. Heidelberger, C. Chaudhuri, N. K.; Danneberg, P.; Mooren, D.; Griesbach, L.; Duschinsky, R.; Schnitzer, R. J.; Pleven, E.; Scheiner, J., Fluorinated Pyrimidines, A New Class of Tumour-Inhibitory Compounds. Nature 1957, 179, 663–666.
8. Doll, R.; Hill, A. B., Smoking and carcinoma of the lung; preliminary report. Br Med J 1950, 2, 739–748.
9. Armstrong, B. K.; Kricker, A.; English, D. R., solarexposure, and skin cancer. The Australasian journal of dermatology 1997, 38 Suppl 1, S1-6.
10. Bhatia, A.; Kumar, Y., Cellular, and molecular mechanisms in cancer immune escape: A comprehensive review. Expert review of clinical immunology 2013, 10.
11. Ward, R. A.; Fawell, S.; Floc’h, N.; Flemington, V.; McKerrecher, D.; Smith, P. D., Challenges and Opportunities in Cancer Drug Resistance. Chemical Reviews 2020.
12. Sun, T.; Zhao, Q.; Zhang, C. Cao, L.; Song, M.; Maimela, N. R.; Liu, S.; Wang, J.; Gao, Q.; Qin, G.; Wang, L.; Zhang, Y., Screening common signaling pathways associated with drug resistance in non-small cell lung cancer via gene expression profile analysis. Cancer Medicine 2019, 8, 3059–3071.
13. Zahreddine, H.; Borden, K., Mechanisms, and insights into drug resistance in cancer. Frontiers in Pharmacology 2013, 4.
14. Liu, R.; Chen, Y.; Liu, G.; Li, C. Song, Y.; Cao, Z.; Li, W.; Hu, J.; Lu, C. The Liu, Y., PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers. Cell Death & Disease 2020, 11, 797.
15. Bokil, A.; Sancho, P., Mitochondrial determinants of chemoresistance. Cancer Drug Resistance 2019, 2, 634–646.
16. Gottesman, M. M.; Lavi, O.; Hall, M. D.; Gillet, J.-P. Toward a Better Understanding of the Complexity of Cancer Drug Resistance. Annual Review of Pharmacology and Toxicology 2016, 56, 85–102.
17. Cree, I. A.; Charlton, P., Molecular chess? Hallmarks of anti-cancer drug resistance. BMC Cancer 2017, 17, 10.
18. Chatterjee, N.; Bivona, T. G., Polytherapy, and Targeted Cancer Drug Resistance. Trends in Cancer 2019, 5, 170–182.
19. Kumar, A.; Singh, U. K.; Chaudhary, A., Targeting autophagy to overcome drug resistance in cancer therapy. Future Medicinal Chemistry 2015, 7, 1535–1542
20. Teicher, B. A., Hypoxia, and drug resistance. Cancer metastasis reviews 1994, 13, 139–68.
21. Minassian, L. M.; Cotechini, T.; Huitema, E.; Graham, C. H., Hypoxia-Induced Resistance to Chemotherapy in Cancer. Advances in experimental medicine and biology in 2019, 1136, 123–139.
22. Sullivan, R.; Paré, G. C. Frederiksen, L. J.; Semenza, G. L.; Graham, C. H., Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity. Molecular Cancer Therapeutics 2008, 7, 1961.
23. Doktorova - Marikova, H.; Hrabeta, J.; Abdel-rahman, M.; Eckschlager, T., Hypoxia-induced chemoresistance in cancer cells: The role of not only HIF-1. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 2015, 159.
24. Sauna, Z.; Smith, M.; Müller, M.; Kerr, K.; Ambudkar, S., The Mechanism of Action of Multidrug-Resistance-Linked P-Glycoprotein. Journal of bioenergetics and biomembranes 2001, 33, 481–91.
25. Choi, C.-H. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell International 2005, 5, 30.
26. Scian, M.; Acchione, M.; Li, M.; Atkins, W. M., Reaction dynamics of ATP hydrolysis catalyzed by P-glycoprotein. Biochemistry 2014, 53, 991–1000.
27. Váradi, A.; Szakács, G.; Bakos, E.; Sarkadi, B., P glycoprotein and the mechanism of multidrug resistance. Novartis Foundation symposium 2002, 243, 54–65; discussion 65–8, 180–5.
28. Sauna, Z. E.; Smith, M. M.; Müller, M.; Kerr, K. M.; Ambudkar, S. V., The mechanism of action of multidrug-resistance-linked P-glycoprotein. J Bioenerg Biomembr 2001, 33, 481–91.
29. Dei, S.; Braconi, L.; Romanelli, M. N.; Teodori, E., Recent advances in the search of BCRP- and dual P-gp/BCRP-based multidrug resistance modulators. Cancer Drug Resistance 2019, 2, 710–743.
30. Shapiro, A. B.; Ling, V., The mechanism of ATP-dependent multidrug transport by P-glycoprotein. Acta Physiol Scand Suppl 1998, 643, 227–234.
31. Kunjachan, S.; Rychlik, B.; Storm, G.; Kiessling, F.; Lammers, T., Multidrug resistance: Physiological principles and nanomedical solutions. Adv Drug Deliv Rev 2013, 65, 1852–1865.
32. Sauna, Z. E.; Ambudkar, S. V., About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work. Molecular Cancer Therapeutics 2007, 6, 13.
33. Callaghan, R.; Luk, F.; Bebawy, M., Inhibition of the Multidrug Resistance P- Glycoprotein: Time for a Change of Strategy? Drug Metabolism and Disposition 2014, 42, 623.
34. Dastvan, R.; Mishra, S.; Peskova, Y. B.; Nakamoto, R. K.; McHaourab, H. S., Mechanism of allosteric modulation of P-glycoprotein by transport substrates and inhibitors. Science 2019, 364, 689.
35. Zhang, M.; Liu, E.; Cui, Y.; Huang, Y., Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer. Cancer Biol Med 2017, 14, 212– 227.
36. Ahmad, J.; Akhter, S.; Greig, N. H.; Kamal, M. A.; Midoux, P.; Pichon, C. Engineered Nanoparticles Against MDR in Cancer: The State of the Art and it is Prospective. Curr Pharm Des 2016, 22, 4360–4373.
37. Majidinia, M.; Mirza-Aghazadeh-Attari, M.; Rahimi, M.; Mihanfar, A.; Karimian, A.; Safa, A.; Yousefi, B., Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons. IUBMB Life 2020, 72, 855–871.
38. Meng, H.; Liong, M.; Xia, T.; Li, Z.; Ji, Z.; Zink, J. I.; Nel, A. E., Engineered Design of Mesoporous Silica Nanoparticles to Deliver Doxorubicin and P-Glycoprotein siRNA to Overcome Drug Resistance in a Cancer Cell Line. ACS Nano 2010, 4, 4539– 4550.
39. He, Q.; Shi, J., MSN Anti-Cancer Nanomedicines: Chemotherapy Enhancement, Overcoming of Drug Resistance, and Metastasis Inhibition. Advanced Materials 2014, 26, 391–411.
40. Bu, H.; Gao, Y.; Li, Y., Overcoming multidrug resistance (MDR) in cancer by nanotechnology. Science China Chemistry 2010, 53, 2226–2232
41. Shen, J.; He, Q.; Gao, Y.; Shi, J.; Li, Y., Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism. Nanoscale 2011, 3, 4314–4322.
42. Zhang, J.; Tang, H.; Liu, Z.; Chen, B., Effects of major parameters of nanoparticles on their physical and chemical properties and the recent application of the nanodrug delivery system in targeted chemotherapy. Int J Nanomedicine 2017, 12, 8483–8493.
43. Zhang, J.; Tang, H.; Liu, Z.; Chen, B., Effects of major parameters of nanoparticles on their physical and chemical properties and the recent application of the nanodrug delivery system in targeted chemotherapy. Int J Nanomedicine 2017, Volume 12, 8483– 8493.
44. Shen, Y. Q. S. Z. H.; Shen, J., Nanotechnology Advances in Medicine: Focus on Cancer. Engineered Science 2019, 7, 1–9.
45. Bharti, C. Nagaich, U.; Pal, A. K.; Gulati, N., Mesoporous silica nanoparticles in the target drug delivery system: A review. Int J Pharm Investig 2015, 5, 124–133.
46. Vallet-Regí, M.; Colilla, M.; Izquierdo-Barba, I.; Manzano, M., Mesoporous Silica Nanoparticles for Drug Delivery: Current Insights. Molecules 2017, 23, 47.
47. Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C. Beck, J. S., Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 1992, 359, 710–712.
48. Fink, W.; Zimpfer-Rechner, C. Thoelke, A.; Figl, R.; Kaatz, M.; Ugurel, S.; Schadendorf, D., Clinical phase II study of pegylated liposomal doxorubicin as second- line treatment in disseminated melanoma. Onkologie 2004, 27, 540–4.
49. Niculescu, V.-C., Mesoporous Silica Nanoparticles for bio-applications. Frontiers in Materials 2020, 7.
50. Narayan, R.; Nayak, U. Y.; Raichur, A. M.; Garg, S., Mesoporous Silica Nanoparticles: A Comprehensive Review of Synthesis and Recent Advances. Pharmaceutics 2018, 10.
51. Wu, S.-H.; , C.-Y.; Lin, H.-P., Synthesis of mesoporous silica nanoparticles. Chemical Society Reviews 2013, 42, 3862–3875.
52. Kankala, R. K.; Han, Y.-H. Na, J.; Lee, C.-H. Sun, Z.; Wang, S.-B. Kimura, T.; Ok,
Y. S.; Yamauchi, Y.; Chen, A.-Z. Wu, K. C. W., Nanoarchitectured Structure, and Surface Biofunctionality of Mesoporous Silica Nanoparticles. Advanced Materials 2020, 32, 1907035.
53. Kankala, R. K.; Zhang, H.; Liu, C.-G. Kanubaddi, K. R.; Lee, C.-H. Wang, S.-B. Cui, W.; Santos, H. A.; Lin, K.; Chen, A.-Z. Metal Species–Encapsulated Mesoporous Silica Nanoparticles: Current Advancements and Latest Breakthroughs. Advanced Functional Materials 2019, 29, 1902652.
54. Jorge, J.; Verelst, M.; Castro, G.; Martines, M., Synthesis parameters for control of mesoporous silica nanoparticles (MSNs). Biointerface Research in Applied Chemistry 2016, 6, 1520.
55. Maleki, A.; Kettiger, H.; Schoubben, A.; Rosenholm, J. M.; Ambrogi, V.; Hamidi, M., Mesoporous silica materials: From Physico-chemical properties to enhanced dissolution of poorly water-soluble drugs. Journal of Controlled Release 2017, 262, 329–347.
56. Cervantes-Martinez, C. V.; Stébé, M.-J. Emo, M.; Lebeau, B.; Lin, J.-L. Hierarchical mesoporous silica templated by the combination of fine emulsion and micelles. Microporous and Mesoporous Materials 2020, 305, 110376.
57. Nam, L.; Coll, C. Erthal, L.; Torre, C. Serrano, D.; Martínez-Máñez, R.; Santos- Martinez, M.; Ruiz-Hernández, E., Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme. Materials (Basel, Switzerland) 2018, 11.
58. Asefa, T.; Tao, Z., Biocompatibility of Mesoporous Silica Nanoparticles.
Chemical Research in Toxicology 2012, 25, 2265–2284.
59. Shi, Y.; Miller, M. L.; Di Pasqua, A. J., Biocompatibility of Mesoporous Silica Nanoparticles? Comments on Inorganic Chemistry 2016, 36, 61–80.
60. Lu, F. Wu, S.-H. Hung, Y.; , C.-Y.The Size Effect on Cell Uptake in Well- Suspended, Uniform Mesoporous Silica Nanoparticles. Small 2009, 5, 1408–1413.
61. Zhu, J.; Liao, L.; Zhu, L.; Zhang, P.; Guo, K.; Kong, J.; Ji, C. Liu, B., Size- dependent cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles toward HeLa cells. Talanta 2013, 107C, 408–415.
62. Tarn, D.; Ashley, C. E.; Xue, M.; Carnes, E. C. Zinc, J. I.; Brinker, C. J., Mesoporous Silica Nanoparticle Nanocarriers: Biofunctionality and Biocompatibility. Accounts of Chemical Research 2013, 46, 792–801.
63. Tang, F.; li, L.; Chen, D., ChemInform Abstract: Mesoporous Silica Nanoparticles:

Synthesis, Biocompatibility, and Drug Delivery. Advanced materials (Deerfield Beach, Fla.) 2012, 24, 1504–34.
64. Vivero-Escoto, J.; Slowing, I.; Trewyn, B.; Lin, V., Mesoporous Silica Nanoparticles for Intracellular Controlled Drug Delivery. Small (Weinheim a der Bergstrasse, Germany) 2010, 6, 1952–67.
65. Meka, A. K.; Jenkins, L. J.; Dàvalos-Salas, M.; Pujara, N.; Wong, K. Y.; Kumeria, T.; Mariadason, J. M.; Popat, A., Enhanced Solubility, Permeability, and Anticancer activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles. Pharmaceutics 2018, 10, 283.
66. Baghirov, H.; Karaman, D.; Viitala, T.; Duchanoy, A.; Lou, Y.-R. Mamaeva, V.; Pryazhnikov, E.; Khiroug, L.; de Lange Davies, C. Sahlgren, C. Rosenholm, J. M., the Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier. PLOS ONE 2016, 11, e0160705.
67. Meka, A. K.; Jenkins, L. J.; Dàvalos-Salas, M.; Pujara, N.; Wong, K. Y.; Kumeria, T.; Mariadason, J. M.; Popat, A., Enhanced Solubility, Permeability, and Anticancer activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles. Pharmaceutics 2018, 10.
68. Shakeran, Z.; Keyhanfar, M.; Varshosaz, J.; Sutherland, D. S., Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for the

delivery methotrexate for application in breast cancer treatment. Materials Science and Engineering: C 2021, 118, 111526.
69. Slowing, I.; Trewyn, B. G.; Lin, V. S. Y., Effect of Surface Functionalization of MCM-41-Type Mesoporous Silica Nanoparticles on the Endocytosis by Human Cancer Cells. Journal of the American Chemical Society 2006, 128, 14792–14793.
70. Hao, N.; Yang, H.; Li, L.; Li, L.; Tang, F., The shape effect of mesoporous silica nanoparticles on intracellular reactive oxygen species in A375 cells. New Journal of Chemistry 2014, 38, 4258–4266.
71. Zhong, H.; Shao, H.; Hong, D.; Ma, T.; Xu, K.; Chen, X.; Han, J.; Sun, J., Shape- Dependent Genotoxicity of Mesoporous Silica Nanoparticles and Cellular Mechanisms. Journal of Nanoscience and Nanotechnology 2016, 16, 2313–2318.
72. Huang, X.; Zhuang, J.; Teng, X.; li, L.; Chen, D.; Yan, X.; Tang, F., The promotion of human malignant melanoma growth by mesoporous silica nanoparticles through decreased reactive oxygen species. Biomaterials 2010, 31, 6142–53.
73. Jafari, S.; Derakhshankhah, H.; Alaei, L.; Fattahi, A.; Varnamkhasti, B.; Saboury, A., Mesoporous silica nanoparticles for therapeutic/diagnostic applications. Biomedicine and Pharmacotherapy 2019, 109, 1100–1111.
74. Pulido-Reyes, G.; Leganes, F. Fernandez-Piñas, F. Rosal, R., Bio-nano interface and environment: A critical review. Environmental Toxicology and Chemistry 2017, 36.

75. Agirre, M.; Zarate, J.; Ojeda, E.; Puras, G.; Desbrieres, J.; Pedraz, J., Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside. Polymers 2014, 6, 1727–1755.
76. Iturrioz, N.; Correa-Duarte, M.; Fanarraga, M., Controlled drug delivery systems for cancer-based on mesoporous silica nanoparticles. Int J Nanomedicine 2019, 2019, 3389—3401.
77. Chang, J.-H. Tsai, P.-H. Chen, W.; Chiou, S.-H. C.-Y. Dual delivery of siRNA and plasmid DNA using mesoporous silica nanoparticles to differentiate induced pluripotent stem cells into dopaminergic neurons. Journal of Materials Chemistry B 2017, 5, 3012–3023.
78. Fortuni, B.; Inose, T.; Ricci, M.; Fujita, Y.; Van Zundert, I.; Masuhara, A.; Fron, E.; Mizuno, H.; Latterini, L.; Rocha, S.; Uji-I, H., Polymeric Engineering of Nanoparticles for Highly Efficient Multifunctional Drug Delivery Systems. Sci Rep 2019, 9, 2666–2666.
79. Argyo, C. Weiss, V.; Bräuchle, C. Bein, T., Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials 2014, 26, 435–451.
80. Bansal, K. K.; Mishra, D. K.; Rosling, A.; Rosenholm, J. M., Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles. Applied Sciences 2020, 10.

81. Haisma, H., Endosomal escape pathways for delivery of biologicals. Human Gene Therapy 2011, 22, A14-A14.
82. Iturrioz-Rodríguez, N.; Correa-Duarte, M. A.; Fanarraga, M. L., Controlled drug delivery systems for cancer based on mesoporous silica nanoparticles. Int J Nanomedicine 2019, 14, 3389–3401.
83. Yang, K.-N. Zhang, C.-Q. Wang, W.; Wang, P. C. Zhou, J.-P. Liang, X.-J.pH- responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment. Cancer Biol Med 2014, 11, 34–43.
84. Chen, H.; Kuang, Y.; Liu, R.; Chen, Z.; Jiang, B.; Sun, Z.; Chen, X.; Li, C., Dual- pH-sensitive mesoporous silica nanoparticle-based drug delivery system for tumor- triggered intracellular drug release. Journal of Materials Science 2018, 53, 10653– 10665.
85. Chen, H.; Zheng, D.; Liu, J.; Kuang, Y.; Li, Q.; Zhang, M.; Ye, H.; Qin, H.; Xu, Y.; Li, C. Jiang, B., pH-Sensitive drug delivery system based on modified dextrin coated mesoporous silica nanoparticles. International Journal of Biological Macromolecules 2016, 85, 596–603.
86. Zhang, M.; Liu, J.; Kuang, Y.; Li, Q.; Zheng, D.-W. Song, Q.; Chen, H.; Chen, X.; Xu, Y.; Li, C. Jiang, B., Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release. International

Journal of Biological Macromolecules 2017, 98.

87. Chen, M.; He, X.; Wang, K.; He, D.; Yang, S.; Qiu, P.; Chen, S., A pH-responsive polymer/mesoporous silica nanocontainer linked through an acid cleavable linker for intracellular controlled release and tumor therapy in vivo. Journal of Materials Chemistry B 2014, 2, 428–436.
88. Lee, C.-H. Cheng, S.-H. Huang, I. P.; Souris, J.; Yang, C.-S. C.-Y. Lo, L.-W. Intracellular pH-Responsive Mesoporous Silica Nanoparticles for the Controlled Release of Anticancer Chemotherapeutics. Angewandte Chemie (International ed. in English) 2010, 49, 8214–9.
89. Li, Q.-L. Xu, S.-H. Zhou, H.; Wang, X.; Dong, B.; Gao, H.; Tang, J.; Yang, Y.-W. In addition, Glutathione Dual-Responsive Dynamic Cross-Linked Supramolecular Network on Mesoporous Silica Nanoparticles for Controlled Anticancer Drug Release. ACS Applied Materials & Interfaces 2015, 7, 28656–28664.
90. Hadipour, P.; Yazdimamaghani, M.; Ghandehari, H., Glutathione-sensitive hollow mesoporous silica nanoparticles for controlled drug delivery. Journal of Controlled Release 2018, 282.
91. Gong, H.; Xie, Z.; Liu, M.; Zhu, H.; Sun, H., Redox-sensitive mesoporous silica nanoparticles functionalized with PEG through a disulfide bond linker for potential anticancer drug delivery. RSC Advances 2015, 5, 59576–59582.

92. Cai, D.; Han, C. Liu, C. Ma, X.; Qian, J.; Zhou, J.; Li, Y.; Sun, Y.; Zhang, C. Zhu, W., Chitosan-capped enzyme-responsive hollow mesoporous silica nanoplatforms for colon-specific drug delivery. Nanoscale Research Letters 2020, 15, 123.
93. Naz, S.; Wang, M.; Han, Y.; Hu, B.; Teng, L.; Zhou, J.; Zhang, H.; Chen, J., Enzyme-responsive mesoporous silica nanoparticles for tumor cells and mitochondria multistage-targeted drug delivery. Int J Nanomedicine 2019, 14, 2533–2542.
94. Ding, J.; Liang, T.; Zhou, Y.; He, Z.; Min, Q.; Jiang, L.; Zhu, J., Hyaluronidase- triggered anticancer drug and siRNA delivery from cascaded targeting nanoparticles for drug-resistant breast cancer therapy. Nano Research 2017, 10, 690–703.
95. Li, E.; Yang, Y.; Hao, G.; Yi, X.; Zhang, S.; Pan, Y.; Xing, B.; Gao, M., Multifunctional Magnetic Mesoporous Silica Nanoagents for in vivo Enzyme- Responsive Drug Delivery and MRI. Nanotheranostics 2018, 2, 233–242.
96. Tao, C.; Zhu, Y., Magnetic Mesoporous Silica Nanoparticles for Potential Delivery of Chemotherapeutic Drugs and Hyperthermia. Dalton Trans. 2014, 43.
127. Hegazy, M.; Zhou, P.; Wu, G.; Wang, L.; Rahoui, N.; Taloub, N.; Huang, X.; Huang, Y., Construction of polymer-coated core-shell magnetic mesoporous silica nanoparticles with triple responsive drug delivery. Polymer Chemistry 2017, 8, 5852– 5864.
97. Meng, D.; Guo, L.; Shi, D.; Sun, X.; Shang, M.; Zhou, X.; Li, J., Charge-

conversion and ultrasound-responsive O-carboxymethyl chitosan nanodroplets for controlled drug delivery. Nanomedicine 2019, 14.
98. Selvasudha, N.; Koumaravelou, K., The Multifunctional Synergistic Effect of Chitosan on Simvastatin Loaded Nanoparticulate Drug Delivery System. Carbohydrate Polymers 2017, 163.
99. Martínez-Carmona, M.; Lozano, D.; Baeza, A.; Colilla, M.; Vallet-Regí, M., A novel visible light-responsive nanosystem for cancer treatment. Nanoscale 2017, 9, 15967–15973.
100. Cheng, C.-A. Chen, W.; Zhang, L.; Wu, H. H.; Zink, J. I., A Responsive Mesoporous Silica Nanoparticle Platform for Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound-Stimulated Cargo Delivery with Controllable Location, Time, and Dose. Journal of the American Chemical Society 2019, 141, 17670–17684.
101. Fan, J.; Du, P.; Wang, X.; Zheng, P.; Zhao, Z.; Duan, A.; Xu, C. Li, J., Ultrasound- assisted synthesis of ordered mesoporous silica FDU-12 with a hollow structure. New Journal of Chemistry 2018, 42, 2381–2384.
102. Wang, X.; Chen, H.; Chen, Y.; Ma, M.; Zhang, K.; Li, F. Zheng, Y.; Zeng, D.; Wang, Q.; Shi, J., Perfluorohexane-Encapsulated Mesoporous Silica Nanocapsules as Enhancement Agents for Highly Efficient High Intensity Focused Ultrasound (HIFU).

Advanced Materials 2012, 24, 785–791.

103. Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A., ROS in cancer therapy: the bright side of the moon. Experimental and Molecular Medicine 2020, 52, 192–203.
104. Jia, P.; Dai, C.; Cao, P.; Sun, D.; Ouyang, R.; Miao, Y., The role of reactive oxygen species in tumor treatment. RSC Advances 2020, 10, 7740–7750.
105. Aggarwal, V.; Tuli, H. S.; Varol, A.; Thakral, F. Yerer, M. B.; Sak, K.; Varol, M.; Jain, A.; Khan, M. A.; Sethi, G., Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements. Biomolecules 2019, 9, 735.
106. Bazhin, A. V.; Philippov, P. P.; Karakhanova, S., Reactive Oxygen Species in Cancer Biology and Anticancer Therapy. Oxidative Medicine and Cellular Longevity 2016, 2016, 4197815.
107. Marina Tamara, N.; Teodora-Monica, N.; Gina, M., Reactive Oxygen Species, Cancer and Anti-Cancer Therapies. Current Chemical Biology 2009, 3, 22–46.
108. Yang, H.; Villani, R. M.; Wang, H.; Simpson, M. J.; Roberts, M. S.; Tang, M.; Liang, X., The role of cellular reactive oxygen species in cancer chemotherapy. Journal of Experimental & Clinical Cancer Research 2018, 37, 266.
109. Yang, B.; Chen, Y.; Shi, J., Reactive Oxygen Species (ROS)-Based Nanomedicine.

Chemical Reviews 2019, 119, 4881–4985.

110. Zorov, D. B.; Juhaszova, M.; Sollott, S. J., Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014, 94, 909–950.
111. Li, X.; Fang, P.; Mai, J.; Choi, E. T.; Wang, H.; Yang, X.-f. Targeting mitochondrial reactive oxygen species as a novel therapy for inflammatory diseases and cancers. Journal of Hematology & Oncology 2013, 6, 19.
112. Dan Dunn, J.; Alvarez, L. A. J.; Zhang, X.; Soldati, T., Reactive oxygen species, and mitochondria: A nexus of cellular homeostasis. Redox Biology 2015, 6, 472–485.
113. Scialò, F. Fernández-Ayala, D. J.; Sanz, A., Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease. Frontiers in Physiology 2017, 8.
114. Sena, L. A.; Chandel, N. S., Physiological roles of mitochondrial reactive oxygen species. Molecular cell 2012, 48, 158–67.
115. N, V. R.; Han, H. S.; Lee, H.; Nguyen, V. Q.; Jeon, S.; Jung, D.-W. Lee, J.; Yi, G.-

R. Park, J. H., ROS-responsive mesoporous silica nanoparticles for MR imaging- guided photo dynamically maneuvered chemotherapy. Nanoscale 2018, 10, 9616–9627.
116. Bahrami, F. Abdekhodaie, M. J.; Behroozi, F. Mehrvar, M., Nano-mesoporous silica for cancer treatment: ROS-responsive and redox-responsive carriers. Journal of Drug Delivery Science and Technology 2020, 57, 101510.

117. Ding, X.; Yu, W.; Wan, Y.; Yang, M.; Hua, C. Peng, N.; Liu, Y., A pH/ROS- responsive, tumor-targeted drug delivery system based on carboxymethyl chitin gated hollow mesoporous silica nanoparticles for anti-tumor chemotherapy. Carbohydrate Polymers 2020, 245, 116493.
118. Bretin, L.; Pinon, A.; Bouramtane, S.; Oak, C. Richard, L.; Perrin, M.-L. Chaunavel, A.; Carrion, C. Bregier, F. Sol, V.; Chaleix, V.; Leger, D. Y.; Liagre, B., Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer. Cancers 2019, 11, 1474.
119. Hamblin, M. R., Upconversion in photodynamic therapy: plumbing the depths.

Dalton Transactions 2018, 47, 8571–8580.

120. Tu, H.-L. Lin, Y.-S. Lin, H.-Y. Hung, Y.; Lo, L.-W. Chen, Y.-F. C.-Y. In vitro Studies of Functionalized Mesoporous Silica Nanoparticles for Photodynamic Therapy. Advanced Materials 2009, 21, 172–177.
121. Wang, Y.; Niu, C. Fan, S.; Li, Y.; Li, X.; Dai, Y.; Shi, J.; Wang, X., indocyanine green Loaded Modified Mesoporous Silica Nanoparticles as an Effective Photothermal Nanoplatform. Int J Mol Sci 2020, 21.
122. Kim, D.; Shin, K.; Kwon, S. G.; Hyeon, T., Synthesis and Biomedical Applications of Multifunctional Nanoparticles. Advanced Materials 2018, 30, 1802309.
123. Yang, H.; Chen, Y.; Chen, Z.; Geng, Y.; Xie, X.; Shen, X.; Li, T.; Li, S.; Wu, C.

Liu, Y., Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites. Biomaterials Science 2017, 5, 1001–1013.
124. Yan, T.; Cheng, J.; Liu, Z.; Cheng, F. Wei, X.; He, J., pH-Sensitive mesoporous silica nanoparticles for chemo-photodynamic combination therapy. Colloids and Surfaces B: Biointerfaces 2018, 161, 442–448.
125. Alfarouk, K. O.; Verduzco, D.; Rauch, C. Muddathir, A. K.; Adil, H. H. B.; Elhassan, G. O.; Ibrahim, M. E.; David Polo Orozco, J.; Cardone, R. A.; Reshkin, S. J.; Harguindey, S., glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience 2014, 1, 777–802.
126. Jiang, B., Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis 2017, 4, 25–27.
127. Ghanbari Movahed, Z.; Rastegari-Pouyani, M.; Mohammadi, M. h. Mansouri, K., Cancer cells change their glucose metabolism to overcome increased ROS: One step from the cancer cell to cancer stem cell? Biomedicine and Pharmacotherapy 2019, 112, 108690.
128. Lee, M. K. S.; Al-Sharea, A.; Shihata, W. A.; Bertuzzo Veiga, C. Cooney, O. D.; Fleetwood, A. J.; Flynn, M. C. Claeson, E.; Palmer, C. S.; Lancaster, G. I.; Henstridge,

D. C. Hamilton, J. A.; Murphy, A. J., Glycolysis Is Required for LPS-Induced Activation and Adhesion of Human CD14+CD16− Monocytes. Frontiers in Immunology 2019, 10.
129. Bhardwaj, V.; He, J., Reactive Oxygen Species, Metabolic Plasticity, and Drug Resistance in Cancer. Int J Mol Sci 2020, 21.
130. Marrache, S.; Dhar, S., The energy blocker inside the power house: mitochondrial targeted delivery of 3-Bromopyruvate. Chemical Science 2015, 6, 1832–1845.
131. Huo, M.; Wang, L.; Chen, Y.; Shi, J., Tumor-selective catalytic nanomedicine by nanocatalyst delivery. Nature Communications 2017, 8, 357
132. Wang, Y.; Huang, H.-Y. Yang, L.; Zhang, Z.; Ji, H., Cetuximab-modified mesoporous silica nanomedicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance. Sci Rep 2016, 6, 25468
133. She, X.; Chen, L.; Velleman, L.; Li, C. He, C. Denman, J.; Wang, T.; Shigdar, S.; Duan, W.; Kong, L., The control of epidermal growth factor grafted on mesoporous silica nanoparticles for targeted delivery. Journal of Materials Chemistry B 2015, 3, 6094–6104.
134. She, X.; Chen, L.; Velleman, L.; li, C. He, L.; Denman, J.; Wang, T.; Shigdar, S.; Duan, W.; Kong, L., The Control of Epidermal Growth Factor Grafted on Mesoporous Silica Nanoparticles for Targeted Delivery. Journal of Materials Chemistry B 2015, 3,

6094–6104.

135. Yang, K.-N. Zhang, C.-Q. Wang, W.; Wang, P. C. Zhou, J.-P. Liang, X.-J.pH- responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment. Cancer Biol Med 2014, 11, 34–43.
136. Chen, H.; Kuang, Y.; Liu, R.; Chen, Z.; Jiang, B.; Sun, Z.; Chen, X.; Li, C., Dual- pH-sensitive mesoporous silica nanoparticle-based drug delivery system for tumor- triggered intracellular drug release. Journal of Materials Science 2018, 53, 10653– 10665.
Chapter-2
1. Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer statistics, 2019. CA: A Cancer Journal for Clinicians 2019, 69, 7–34.
2. Guo, Z.; Zheng, K.; Tan, Z.; Liu, Y.; Zhao, Z.; Zhu, G.; Ma, K.; Cui, C. Wang, L.; Kang, T., Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug delivery, and photodynamic therapy. Journal of Materials Chemistry B 2018, 6, 7750–7759.
3. Aniogo, E. C. Plackal Adimuriyil George, B.; Abrahamse, H., The role of photodynamic therapy in multidrug-resistant breast cancer. Cancer Cell International 2019, 19, 91.
4. Huang, Z.; Hsu, Y.-C. Li, L.-B. Wang, L.-W. Song, X.-D. Yow, C. M. N.; Lei, X.; Musani, A. I.; Luo, R.-C. Day, B. J., Photodynamic therapy of cancer — Challenges of multidrug resistance. Journal of Innovative Optical Health Sciences 2014, 08, 1530002.
5. Holohan, C. Van Schaeybroeck, S.; Longley, D. B.; Johnston, P. G., Cancer drug resistance: an evolving paradigm. Nature Reviews Cancer 2013, 13, 714–726.
6. Nanayakkara, A. K.; Follit, C. A.; Chen, G.; Williams, N. S.; Vogel, P. D.; Wise, J. G., Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug-resistant tumor cells. Scientific Reports 2018, 8, 967.
7. Kapse-Mistry, S.; Govender, T.; Srivastava, R.; Yergeri, M., Nano-drug delivery

in reversing multidrug resistance in cancer cells. Frontiers in Pharmacology 2014, 5.

8. Capella, M. A.; Capella, L. S., A light in multidrug resistance: photodynamic treatment of multidrug-resistant tumors. Journal of biomedical science 2003, 10, 361.
9. Zhang, W.; Shen, J.; Su, H.; Mu, G.; Sun, J.-H. Tan, C.-P. Liang, X.-J. Ji, L.-N. Mao, Z.-W. Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance. ACS Applied Materials & Interfaces 2016, 8, 13332–13340.
10. Park, S.; Park, H.; Jeong, S.; Yi, B. G.; Park, K.; Key, J., Hyaluronic Acid- Conjugated Mesoporous Silica Nanoparticles Loaded with Dual Anticancer Agents for Chemophotodynamic Cancer Therapy. Journal of Nanomaterials 2019, 2019, 3481397.
11. Hong, S. H.; Choi, Y., Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents. J Pharm Investig 2018, 48, 3–17.
12. Wei, X.; Liu, L.; Guo, X.; Wang, Y.; Zhao, J.; Zhou, S., Light-Activated ROS- Responsive Nanoplatform Codelivering Apatinib and doxorubicin for Enhanced Chemo-Photodynamic Therapy of Multidrug-Resistant Tumors. ACS Applied Materials & Interfaces 2018, 10, 17672–17684.
13. Tang, X.-l. Jing, F. Lin, B.-l. Cui, S.; Yu, R.-t. Shen, X.-d. Wang, T.-w.pH- Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy. ACS Applied Materials & Interfaces 2018, 10,

15001–15011.

14. Hu, J.-J. Lei, Q.; Zhang, X.-Z. Recent advances in photonanomedicines for enhanced cancer photodynamic therapy. Progress in Materials Science 2020, 114, 100685.
15. Wang, Z.; Deng, Z.; Zhu, G., Emerging platinum (iv) prodrugs to combat cisplatin resistance: from isolated cancer cells to the tumor microenvironment. Dalton Transactions 2019, 48, 2536–2544.
16. Kim, H.; Wu, X.; Lee, J., SLC31 (CTR) family of copper transporters in health and disease. Mol Aspects Med 2013, 34, 561–570.
17. Sinani, D.; Kim, H.; Lee, J., Distinct Mechanisms for Ctr1-mediated Copper and Cisplatin Transport. The Journal of biological chemistry 2007, 282, 26775–85.
18. Martinho, N.; Santos, T. C. B.; Florindo, H. F. Silva, L. C. Cisplatin-Membrane Interactions and Their Influence on Platinum Complex Activity and Toxicity. Frontiers in Physiology 2019, 9.
19. Dasari, S.; Tchounwou, P. B., Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014, 740, 364–378.
20. Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kemp, O.; Castedo, M.; Kroemer, G., Molecular mechanisms of cisplatin resistance. Oncogene 2012, 31, 1869–1883.

21. Shen, D.-W. Pouliot, L. M.; Hall, M. D.; Gottesman, M. M., Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev 2012, 64, 706–721.
22. Muley, H.; Fadó, R.; Rodríguez-Rodríguez, R.; Casals, N., Drug uptake-based chemoresistance in breast cancer treatment. Biochemical Pharmacology 2020, 177, 113959.
23. Yellepeddi, V. K.; Vangara, K. K.; Palakurthi, S., Poly(amido) amine (PAMAM) dendrimer–cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells. Journal of Nanoparticle Research 2013, 15, 1897.
24. Kilari, D.; Guancial, E.; Kim, E. S., Role of copper transporters in platinum resistance. World J Clin Oncol 2016, 7, 106–113.
25. Choi, M.-K.; Kim, D.-D., Platinum transporters, and drug resistance. Archives of Pharmacal Research 2006, 29, 1067–1073.
26. Zhang, W.; Shen, J.; Su, H.; Mu, G.; Sun, J. H.; Tan, C. P.; Liang, X. J.; Ji, L. N.; Mao, Z. W., Co-Delivery of Cisplatin prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance. ACS Appl Mater Interfaces 2016, 8, 13332–40.
27. Hewlings, S. J.; Kalman, D. S., Curcumin: A Review of Its Effects on Human Health. Foods 2017, 6, 92.

28. Kielbik, A.; Wawryka, P.; Przystupski, D.; Rossowska, J.; Szewczyk, A.; Saczko, J.; Kulbacka, J.; Chwiłkowska, A., Effects of Photosensitization of Curcumin in Human Glioblastoma Multiforme Cells. In Vivo 2019, 33, 1857–1864.
29. Kazantzis, K. T.; Koutsonikoli, K.; Mavroidi, B.; Zachariadis, M.; Alexiou, P.; Pelecanos, M.; Politopoulos, K.; Alexandratou, E.; Sagnou, M., Curcumin derivatives as photosensitizers in photodynamic therapy: photophysical properties and in vitro studies with prostate cancer cells. Photochemical and Photobiological Sciences 2020, 19, 193–206.
30. Wei, C. Zhang, F. Song, L.; Chen, X.; Meng, X., the Photosensitization effect of curcumin for controlling plant pathogen Botrytis cinerea in postharvest apple. Food Control 2020, 107683.
31. Kuthati, Y.; Kankala, R. K.; Bush, P.; Lin, S.-X. Deng, J.-P.; , C.-Y. Lee, C.-H. Phototherapeutic spectrum expansion through the synergistic effect of mesoporous silica trio-nanohybrids on the antibiotic-resistant gram-negative bacterium. Journal of Photochemistry and Photobiology B: Biology 2017, 169, 124–133.
32. Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T.; Wang, S., Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine: Nanotechnology, Biology and Medicine 2015, 11, 313– 327.

33. Ghosh, S., Chapter 9-Mesoporous Silica-Based Nano Drug-Delivery System Synthesis, Characterization, and Applications. In Nanocarriers for Drug Delivery, Mohapatra, S. S.; Ranjan, S.; Dasgupta, N.; Mishra, R. K.; Thomas, S., Eds. Elsevier: 2019; pp 285–317.
34. Xu, C.; Lei, C.; Yu, C., Mesoporous Silica Nanoparticles for Protein Protection and Delivery. Frontiers in Chemistry 2019, 7.
35. Argyo, C. Weiss, V.; Bräuchle, C. Bein, T., Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials 2014, 26, 435–451.
36. Wang, Y.; Zhao, Q.; Han, N.; Bai, L.; Li, J.; Liu, J.; Che, E.; Hu, L.; Zhang, Q.; Jiang, T.; Wang, S., Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine 2015, 11, 313–327.
37. He, Q.; Gao, Y.; Zhang, L.; Zhang, Z.; Gao, F. Ji, X.; Li, Y.; Shi, J., A pH- responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multidrug resistance. Biomaterials 2011, 32, 7711–7720.
38. Guo, Z.; Zheng, K.; Tan, Z.; Liu, Y.; Zhao, Z.; Zhu, G.; Ma, K.; Cui, C. Wang, L.; Kang, T., Overcoming drug resistance with functional mesoporous titanium dioxide nanoparticles combining targeting, drug delivery, and photodynamic therapy. Journal of Materials Chemistry B 2018, 6.

39. Spring, B.; Rizvi, I.; Xu, N.; Hasan, T., The role of photodynamic therapy in overcoming cancer drug resistance. Photochem. Photobiol. Sci. 2015, 14.
40. Hanafi-Bojd, M. Y.; Ansari, L.; Mosaffa, F. Malaekeh-Nikouei, B., The effect of mesoporous silica nanoparticles loaded with epirubicin on drug-resistant cancer cells. Nanomedicine Journal 2017, 4, 135–141.
41. Florek, J.; Caillard, R.; Kleitz, F. Evaluation of mesoporous silica nanoparticles for oral drug delivery – current status and perspective of MSN's drug carriers. Nanoscale 2017, 9, 15252–15277.
42. Han, Y.; Ying, J. Y., Generalized Fluorocarbon-Surfactant-Mediated Synthesis of Nanoparticles with Various Mesoporous Structures. Angewandte Chemie International Edition 2005, 44, 288–292.
43. Li, Y.; Song, F. Guo, Y.; Cheng, L.; Chen, Q., Multifunctional Amine Mesoporous Silica Spheres Modified with Multiple Amine as Carriers for Drug Release. Journal of Nanomaterials 2018, 2018, 1726438.
44. He, Y.; Luo, L.; Liang, S.; Long, M.; Xu, H., Amino-functionalized mesoporous silica nanoparticles as efficient carriers for anticancer drug delivery. Journal of Biomaterials Applications 2017, 32, 524–532.
45. Amesh, P.; Suneesh, A. S.; Venkatesan, K. A.; Chandra, M.; Ravindranath, N. A., High capacity amidic succinic acid-functionalized mesoporous silica for the adsorption

of uranium. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2020, 602, 125053.
46. Lee, C.-H. Cheng, S.-H. Huang, I. P.; Souris, J. S.; Yang, C.-S. You, C.-Y. Lo, L.-

W. Intracellular pH-Responsive Mesoporous Silica Nanoparticles for the Controlled Release of Anticancer Chemotherapeutics. Angewandte Chemie International Edition 2010, 49, 8214–8219.
47. Kuo, Y.-M. Kuthati, Y.; Kankala, R. K.; Wei, P.-R. Weng, C. Sung, P.-J. Liu, C.-L. C.-Y. Lee, C.-H. Layered Double Hydroxide Nanoparticles to Enhance Organ-Specific Targeting and Anti-Proliferative Effect of Cisplatin. Journal of Materials Chemistry B 2015, 3.
48. Lin, C.-H. Cheng, S.-H. Liao, w. n. Wei, P.-R. Sung, P.-J. Weng, C. Lee, C.-H. Mesoporous silica nanoparticles for the improved anticancer efficacy of cis-platin. International journal of pharmaceutics 2012, 429, 138–47.
49. Basotra, M.; Singh, S.; Gulati, M., Development, and Validation of a Simple and Sensitive Spectrometric Method for Estimation of Cisplatin Hydrochloride in Tablet Dosage Forms: Application to Dissolution Studies. ISRN Analytical Chemistry 2013, 2013.
50. Dodangeh, M.; Grabchev, I.; Gharanjig, K.; Staneva, D.; Tang, R.-C. Sheridan, M., Modified PAMAM dendrimers as a matrix for the photo stabilization of curcumin. New

Journal of Chemistry 2020.

51. Cheng, S.-H. Lee, C.-H. Yang, C.-S. Tseng, F.-G. You, C.-Y. Lo, L.-W. Mesoporous silica nanoparticles functionalized with an oxygen-sensing probe for cell photodynamic therapy: Potential cancer theranostics. Journal of Materials Chemistry - J MATER CHEM 2009, 19.
52. Strober, W., Trypan blue exclusion test of cell viability. Current protocols in immunology 2001, Appendix 3, Appendix 3B.
53. Zhang, Z.; Huang, C. Zhang, L.; Guo, Q.; Qin, Y.; Fan, F. Li, B.; Xiao, B.; Zhu, D.; Zhang, L., pH-Sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy. Acta Pharmaceutica Sinica B 2020.
54. He, Q.; Shi, J., Mesoporous silica nanoparticle-based nanodrug delivery systems: synthesis, controlled drug release, and delivery, pharmacokinetics, and biocompatibility. Journal of Materials Chemistry 2011, 21, 5845–5855.
55. Mahdi, K.; Hamed, M.; Masoumeh, A.; Parham, S.-Z. Michael, R. H., Smart mesoporous silica nanoparticles for controlled-release drug delivery. Nanotechnology Reviews 2016, 5, 195–207.
56. Zheng, N.; Chen, L.; Xie, L.; Cui, M.; Li, S.; xu, l. The effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin. Pharmaceutics

2018, 11, 4.

57. Deljoo, S.; Rabiee, N.; Rabiee, M., Curcumin-hybrid Nanoparticles in Drug Delivery System (Review). Asian Journal of Nanosciences and Materials 2019, 2, 66– 91.
58. Jambhrunkar, S.; Karmakar, S.; Popat, A.; Yu, M.; Yu, C. Mesoporous silica nanoparticles enhance the cytotoxicity of curcumin. RSC Advances 2013, 4, 709–712.
59. Sundarraj, S., 158P - Targeting Efficiency and Biodistribution of EGFR- Conjugated Mesoporous Silica Nanoparticles for Cisplatin Delivery in Nude Mice with Lung Cancer. Annals of Oncology 2012, 23, ix70-ix71.
60. Li, H.; Yu, H.; Zhu, C. Hu, J.; Du, M.; Zhang, F. Yang, D., Cisplatin and doxorubicin dual-loaded mesoporous silica nanoparticles for controlled drug delivery. RSC Advances 2016, 6, 94160–94169.
61. Wang, C. Song, X.; Shang, M.; Zou, W.; Zhang, M.; Wei, H.; Shao, H., Curcumin exerts cytotoxicity dependent on reactive oxygen species accumulation in non-small- cell lung cancer cells. Future Oncology 2019, 15.
Chapter-3

1. Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer statistics, 2020. CA: A Cancer Journal for Clinicians 2020, 70, 7–30.
2. Pucci, C. Martinelli, C. Ciofani, G., Innovative approaches for cancer treatment: current perspectives and new challenges. Ecancermedicalscience 2019, 13, 961–961.
3. Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B., The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull 2017, 7, 339–348.
4. Wang, J.; Seebacher, N.; Shi, H.; Kan, Q.; Duan, Z., Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget 2017, 8, 84559– 84571.
5. Ji, X.; Lu, Y.; Tian, H.; Meng, X.; Wei, M.; Cho, W. C. Chemoresistance mechanisms of breast cancer and their countermeasures. Biomedicine and Pharmacotherapy 2019, 114, 108800.
6. Wang, X.; Zhang, H.; Chen, X., Drug resistance, and combating drug resistance in cancer. Cancer Drug Resistance 2019, 2, 141–160.
7. Pan, L.; Liu, J.; He, Q.; Wang, L.; Shi, J., Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles. Biomaterials 2013, 34, 2719–30.

8. Wang, S.; Liu, X.; Chen, S.; Liu, Z.; Zhang, X.; Liang, X.-J. Li, L., Regulation of Ca2+ Signaling for Drug-Resistant Breast Cancer Therapy with Mesoporous Silica Nanocapsule Encapsulated Doxorubicin/siRNA Cocktail. ACS Nano 2019, 13, 274– 283.
9. Pan, L.; Liu, J.; He, Q.; Wang, L.; Shi, J., Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles. Biomaterials 2013, 34, 2719–2730.
10. Liu, J.; Li, Q.; Zhang, J.; Huang, L.; Qi, C. Xu, L.; Liu, X.; Wang, G.; Wang, L.; Wang, Z., Safe and Effective Reversal of Cancer Multidrug Resistance Using Sericin- Coated Mesoporous Silica Nanoparticles for Lysosome-Targeting Delivery in Mice. Small 2017, 13, 1602567.
11. Castillo, R. R.; Colilla, M.; Vallet-Regí, M., Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer. Expert Opinion on Drug Delivery 2017, 14, 229–243.
12. Liu, M.; Fu, M.; Yang, X.; Jia, G.; Shi, X.; Ji, J.; Liu, X.; Zhai, G., Paclitaxel, and quercetin co-loaded functional mesoporous silica nanoparticles overcoming multidrug resistance in breast cancer. Colloids and Surfaces B: Biointerfaces 2020, 196, 111284.
13. Zhou, L.; Wang, H.; Li, Y., Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance. Theranostics 2018, 8, 1059–1074.

14. Siddiqi, K. S.; Husen, A.; Rao, R. A. K., A review of the biosynthesis of silver nanoparticles and their biocidal properties. Journal of Nanobiotechnology 2018, 16, 14.
15. Syafiuddin, A.; Salmiati; Salim, M. R.; Being Hong Kueh, A.; Hadibarata, T.; Nur, H., A Review of Silver Nanoparticles: Research Trends, Global Consumption, Synthesis, Properties, and Future Challenges. Journal of the Chinese Chemical Society 2017, 64, 732–756.
16. Perde-Schrepler, M.; Florea, A.; Brie, I.; Virag, P.; Fischer-Fodor, E.; Vâlcan, A.; Gurzău, E.; Lisencu, C. Maniu, A., Size-Dependent Cytotoxicity and Genotoxicity of Silver Nanoparticles in Cochlear Cells In Vitro. Journal of Nanomaterials 2019, 2019, 6090259.
17. AshaRani, P. V.; Low Kah Mun, G.; Hand, M. P.; Valiyaveettil, S., Cytotoxicity, and Genotoxicity of Silver Nanoparticles in Human Cells. ACS Nano 2009, 3, 279–290.
18. Souza, T. A. J.; Franchi, L. P.; Rosa, L. R.; da Veiga, M. A. M. S.; Takahashi, C. S., Cytotoxicity, and genotoxicity of silver nanoparticles of different sizes in CHO-K1 and CHO-XRS5 cell lines. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2016, 795, 70–83.
19. Zhang, L.; Wu, L.; Si, Y.; Shu, K., Size-dependent cytotoxicity of silver nanoparticles to Azotobacter vinelandii: Growth inhibition, cell injury, oxidative stress, and internalization. PLOS ONE 2018, 13, e0209020.

20. Akter, M.; Sikder, M. T.; Rahman, M. M.; Ullah, A. K. M. A.; Hossain, K. F. B.; Banik, S.; Hosokawa, T.; Saito, T.; Kurasaki, M., A systematic review of silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives. Journal of Advanced Research 2018, 9, 1–16.
21. Chairuangkitti, P.; Lawanprasert, S.; Roytrakul, S.; Aueviriyavit, S.; Phummiratch, D.; Kulthong, K.; Chanvorachote, P.; Maniratanachote, R., Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways. Toxicology in Vitro 2013, 27, 330–338.
22. El-Hussein, A.; Hamblin, M. R., ROS generation and DNA damage with photo- inactivation mediated by silver nanoparticles in lung cancer cell line. IET Nanobiotechnol 2017, 11, 173–178.
23. He, D.; Jones, A. M.; Garg, S.; Pham, A. N.; Waite, T. D., Silver Nanoparticle−Reactive Oxygen Species Interactions: Application of the Charging−Discharging Model. The Journal of Physical Chemistry C 2011, 115, 5461– 5468.
24. Hossain, Z.; Huq, F., Studies on the interaction between Ag+ and DNA. Journal of Inorganic Biochemistry 2002, 91, 398–404.
25. Piao, M. J.; Kang, K. A.; Lee, I. K.; Kim, H. S.; Kim, S.; Choi, J. Y.; Choi, J.; Hyun, J. W., Silver nanoparticles induce oxidative cell damage in human liver cells

through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicology letters 2011, 201, 92–100.
26. Piao, M. J.; Kim, K. C. Choi, J.-Y. Choi, J.; Hyun, J. W., Silver nanoparticles down-regulate Nrf2-mediated 8-oxoguanine DNA glycosylase 1 through inactivation of extracellular regulated kinase and protein kinase B in human Chang liver cells. Toxicology letters 2011, 207, 143–148.
27. Maurer, L. L.; Meyer, J. N., A systematic review of the evidence for silver nanoparticle-induced mitochondrial toxicity. Environmental Science: Nano 2016, 3, 311–322.
28. Flores-López, L. Z.; Espinoza-Gómez, H.; Somanathan, R., Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review. Journal of Applied Toxicology 2019, 39, 16–26.
29. Holmila, R. J.; Vance, S. A.; King, S. B.; Tsang, A. W.; Singh, R.; Furdui, C. M., Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation. Antioxidants 2019, 8.
30. Onodera, A.; Nishiumi, F. Kakiguchi, K.; Tanaka, A.; Tanabe, N.; Honma, A.; Yayama, K.; Yoshioka, Y.; Nakahira, K.; Yonemura, S.; Yanagihara, I.; Tsutsumi, Y.; Kawai, Y., Short-term changes in intracellular ROS localization after the silver nanoparticles exposure depending on particle size. Toxicology Reports 2015, 2, 574–

579.

31. Zorov, D. B.; Juhaszova, M.; Sollott, S. J., Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014, 94, 909–950.
32. Kausar, S.; Wang, F. Cui, H., The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases. Cells 2018, 7, 274.
33. Yoboue, E. D.; Devin, A., Reactive Oxygen Species-Mediated Control of Mitochondrial Biogenesis. International Journal of Cell Biology 2012, 2012, 403870.
34. Guerra, F. Arbini, A. A.; Moro, L., Mitochondria and cancer chemoresistance.

Biochimica et Biophysica Acta (BBA) - Bioenergetics 2017, 1858, 686–699.

35. Lee, W.; Choi, H.-I. Kim, M.-J. Park, S.-Y. Depletion of mitochondrial DNA up- regulates the expression of the MDR1 gene via an increase in mRNA stability. Experimental and Molecular Medicine 2008, 40, 109–117.
36. Gopisetty, M. K.; Kovács, D.; Igaz, N.; Rónavári, A.; Bélteky, P.; Rázga, Z.; Venglovecz, V.; Csoboz, B.; Boros, I. M.; Kónya, Z.; Kiricsi, M., Endoplasmic reticulum stress: a major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells. Journal of Nanobiotechnology 2019, 17, 9.
37. Thuesombat, P.; Hannongbua, S.; Ekgasit, S.; Chadchawan, S., Effects of Silver

Nanoparticles on Hydrogen Peroxide Generation and Antioxidant Enzyme Responses in Rice. Journal of Nanoscience and Nanotechnology 2016, 16, 8030–8043.
38. Sigg, L.; Lindauer, U., Silver nanoparticle dissolution in the presence of ligands and hydrogen peroxide. Environ Pollut 2015, 206, 582–587.
39. Gao, Y.; Chen, Y.; Ji, X.; He, X.; Yin, Q.; Zhang, Z.; Shi, J.; Li, Y., Controlled Intracellular Release of Doxorubicin in Multidrug-Resistant Cancer Cells by Tuning the Shell-Pore Sizes of Mesoporous Silica Nanoparticles. ACS Nano 2011, 5, 9788– 9798.
40. Chen, A. M.; Zhang, M.; Wei, D.; Stueber, D.; Taratula, O.; Minko, T.; He, H., Co- delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells. Small (Weinheim an der Bergstrasse, Germany) 2009, 5, 2673–2677.
41. Wang, X.; Liu, Y.; Wang, S.; Shi, D.; Zhou, X.; Wang, C. Wu, J.; Zeng, Z.; Li, Y.; Sun, J.; Wang, J.; Zhang, L.; Teng, Z.; Lu, G., CD44-Engineered Mesoporous Silica Nanoparticles for Overcoming Multidrug Resistance in Breast Cancer. Applied Surface Science 2015, 332.
42. Han, L.; Wei, H.; Tu, B.; Zhao, D., A facile one-pot synthesis of uniform core-shell silver nanoparticle@mesoporous silica nanospheres. Chemical Communications 2011, 47, 8536–8538.

43. Li, Y.; Song, F. Guo, Y.; Cheng, L.; Chen, Q., Multifunctional Amine Mesoporous Silica Spheres Modified with Multiple Amine as Carriers for Drug Release. Journal of Nanomaterials 2018, 2018, 1726438.
44. Nowicki, W., Structural studies of complexation of Cu(II) with amino silane- modified silica surface in a heterogeneous system in various pH. Applied Surface Science 2019, 469, 566–572.
45. Kang, C. Li, W.; Tan, L.; Li, H.; Wei, C. Tang, Y., Highly ordered metal ion imprinted mesoporous silica particles exhibiting specific recognition and fast adsorption kinetics. Journal of Materials Chemistry A 2013, 1, 7147–7153.
46. Khdary, N. H.; Ghanem, M. A.; Abdesalam, M. E.; Al-Garadah, M. M., Sequestration of CO2 using Cu nanoparticles supported on spherical and rod-shaped mesoporous silica. Journal of Saudi Chemical Society 2018, 22, 343–351.
47. Shao, D.; Zhang, X.; Liu, W.; Zhang, F. Zheng, X.; Qiao, P.; Li, J.; Dong, W.; Chen, L., Janus Silver-Mesoporous Silica Nanocarriers for SERS Traceable and pH-Sensitive Drug Delivery in Cancer Therapy. ACS applied materials & interfaces 2016, 8 7, 4303– 8.
48. Yang, X.; Xiong, J.; Qiu, P.; Chen, M.; He, D.; He, X.; Wang, K.; Tang, J., Synthesis of a core/satellite-like multifunctional nanocarrier for pH- and NIR-triggered intracellular chemothermal therapy and tumor imaging. RSC Advances 2017, 7, 7742–

7752.

49. Wang, Y.; Ding, X.; Chen, Y.; Guo, M.; Zhang, Y.; Guo, X.; Gu, H., Antibiotic- Loaded, Silver Core-Embedded Mesoporous Silica Nanovehicles as a Synergistic Antibacterial Agent for the Treatment of Drug-Resistant Infections. Biomaterials 2016, 101, 207–216.
50. Zhang, K.; Lam, K.-F. Albela, B.; Xue, T.; Khrouz, L.; Hou, Q.-W.The; Yuan, E.; He, M.-Y. Bonneviot, L., Mononuclear-Dinuclear Equilibrium of Grafted Copper Complexes Confined in the Nanochannels of MCM-41 Silica. Chemistry (Weinheim an der Bergstrasse, Germany) 2011, 17, 14258–66.
51. Zhang, J.; Luz, Z.; Goldfarb, D., EPR Studies of the Formation Mechanism of the Mesoporous Materials MCM-41 and MCM-50. The Journal of Physical Chemistry B 1997, 101, 7087–7094.
52. Cheng, Y.; Zhang, A.-Q. Hu, J.-J. He, F. Zeng, X., Multifunctional Peptide- Amphiphile End-Capped Mesoporous Silica Nanoparticles for Tumor Targeting Drug Delivery. ACS Applied Materials & Interfaces 2016, 9.
53. Tsanova, P.; Donkova, B.; Karadjova, I.; Dushkin, C. Synthesis of starch-stabilized silver nanoparticles and their application as a surface plasmon resonance-based sensor of hydrogen peroxide. Colloids and Surfaces A-physicochemical and Engineering Aspects - COLLOID SURFACE A 2011, 382, 203–210.

54. Nishimoto, M.; Abe, S.; Yonezawa, T., Preparation of Ag nanoparticles using hydrogen peroxide as a reducing agent. New Journal of Chemistry 2018, 42, 14493– 14501.
55. Arakawa, H.; Neault, J. F. Tajmir-Riahi, H. A., Silver (I) Complexes with DNA and RNA Studied by Fourier transform infrared spectroscopy and capillary electrophoresis. Biophysical Journal 2001, 81, 1580–1587.
56. Wu, H.; Zhang, Y.; Chen, C. Zhang, J.; Bai, Y.; Shi, F. Wang, X., DNA-binding studies and antioxidant activities of two-, three- and four-coordinate silver (i) complexes containing bis (2-benzimidazolyl) aniline derivatives. New Journal of Chemistry 2014, 38, 3688–3698.
57. Duo, Y.; Li, Y.; Chen, C. Liu, B.; Wang, X.; Zeng, X.; Chen, H., DOX-loaded pH- sensitive mesoporous silica nanoparticles coated with PDA and PEG induce pro-death autophagy in breast cancer. RSC Advances 2017, 7, 39641–39650.
58. Moodley, T.; Singh, M., Sterically stabilized Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy. Molecules 2020, 25, 742.
59. Luo, W.; Xu, X.; Zhou, B.; He, P.; Li, Y.; Liu, C. The formation of enzymatic/redox-switching navigates on mesoporous silica nanoparticles for anticancer drug delivery. Materials Science and Engineering: C 2019, 100, 855–861.

60. Qu, Q.; Ma, X.; Zhao, Y., Targeted Delivery of Doxorubicin to Mitochondria Using Mesoporous Silica Nanoparticle Nanocarriers. Nanoscale 2015, 7.
61. Luo, G.-F. Chen, W.-H. Liu, Y.; Lei, Q.; Zhuo, R.-X. Zhang, X.-Z. Multifunctional Enveloped Mesoporous Silica Nanoparticles for Subcellular Co-delivery of Drug and Therapeutic Peptide. Scientific Reports 2014, 4, 6064.
62. Chen, H.; Wang, Y.; Yao, Y.; Qiao, S.; Wang, H.; Tan, N., Sequential Delivery of Cyclopeptide RA-V and Doxorubicin for Combination Therapy on Resistant Tumor and In Situ Monitoring of Cytochrome c Release. Theranostics 2017, 7, 3781–3793.
63. Qu, Q.; Ma, X.; Zhao, Y., the Anticancer Effect of α-Tocopheryl Succinate Delivered by Mitochondria-Targeted Mesoporous Silica Nanoparticles. ACS Applied Materials & Interfaces 2016, 8, 34261–34269.
64. Li, Q.; Huang, Y., Mitochondrial targeted strategies and their application for cancer and other diseases treatment. Journal of Pharmaceutical Investigation 2020, 50, 271–293.
65. Sun, K.; Gao, Z.; Zhang, Y.; Wu, H.-S. You, C. Wang, S.; An, P.-J. Sun, C. Sun, B., Enhanced highly toxic reactive oxygen species levels by iron oxide core-shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy. Journal of Materials Chemistry B 2018, 6.
66. Li, X.-J. Li, W.-T. Li, Z.-H.-R. Zhang, L.-P. Gai, C.-C. Zhang, W.-F. Ding, D.-J.

Iron-Chelated Polydopamine Decorated Doxorubicin-Loaded Nanodevices for Reactive Oxygen Species Enhanced Cancer Combination Therapy Front Pharmacol [Online], 2019, p. 75. PubMed. http://europepmc.org/abstract/MED/30787876
https://doi.org/10.3389/fphar.2019.00075 https://europepmc.org/articles/PMC6372743 https://europepmc.org/articles/PMC6372743?pdf=render (accessed 2019).
67. Yang, B.; Chen, Y.; Shi, J., Reactive Oxygen Species (ROS)-Based Nanomedicine.

Chemical Reviews 2019, 119, 4881–4985.

68. Sun, K.; Gao, Z.; Zhang, Y.; Wu, H.; You, C. Wang, S.; An, P.; Sun, C. Sun, B., Enhanced highly toxic reactive oxygen species levels from iron oxide core-shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy. Journal of Materials Chemistry B 2018, 6, 5876–5887.