Development of Silica Based Nanoparticles for Multimodal Therapeutic Delivery

1 online resource (178 pages) : PDF

2022

University of North Carolina at Charlotte

Chronic diseases like cancer are characterized by complex interactions between multiple pathways leading to treatment resistance and invasiveness. Repeated cycles of cytotoxic monotherapies are susceptible to drug resistance induced by the upregulation of cytoprotective genes. Some common mechanisms that promote sustenance of cancer include hypoxia, antioxidant response, anti-apoptotic protein synthesis, angiogenesis, and metastatic potential. Combinations that rely on different therapeutic approaches such as chemo, photodynamic and gene therapy with independent mechanisms of action remarkably enhance the therapeutic efficacy against cancer. In addition, downregulation of survival mechanisms alongside administration of mainstay cytotoxic treatments is a promising strategy for combination therapy. The main challenge behind the use of combination therapy is the lack of efficient delivery systems that allows the spatiotemporal release required for co-delivery of multiple therapeutic agents. Recently, nanoparticulate delivery system have become a successful alternative for making stable formulations of multiple drugs and for the protection of nucleic acid therapeutics against enzymatic degradation. In particular, silica-based nanoparticles (SiNP) can be engineered to carry different types of therapeutic agents, to enhance the target-specificity and to avoid side effects associated with the drugs. The design, synthesis and characterization of mesoporous silica and hybrid organosilica nanoparticles comprising bimodal combinations of small molecule drugs, photosensitizers (PSs), and/or siRNA, are discussed in this Thesis. The therapeutic performance of the synthesized nanomedicines is evaluated in cancer cell lines.

doctoral dissertations

Nanoscience

Ph.D.

Nanoscale Science

Vivero-Escoto, Juan

Afonin, Kirill
Troutman, Jerry
Chi, Richard
Trammell, Susan
Nesmelov, Yuri

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2022.

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Vadarevu_uncc_0694D_13027

http://hdl.handle.net/20.500.13093/etd:2744