Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for Cancer Nanomedicine

Abstract

It is well established that cancer is one of the leading causes of death globally. Its complete eradication requires early detection and intensive drug treatment. In many cases it might also require surgery. Unfortunately, current medicine is still more focused on cancer treatment rather than elimination of its reason. The mechanism of tumor emergence and development is quite complicated, although, we are constantly advancing in this field. Nanomedicine is envisioned as the silver bullet against cancer. Thus, nanoscale systems with therapeutic and diagnostic modalities can simultaneously perform several functions: accurate detection of tumor site, precise targeting, and controlled drug release inside abnormal cells and tissues while being nontoxic to healthy ones. Moreover, surface modification of such nanoparticles allows them to be invisible to the immune system and have longer blood circulating time. The performed research in this dissertation is completely based on hybrid organicinorganic bridged silsesquioxane (also known as organosilica) nanomaterials, therefore comprising "soft" organic/bioorganic part which can imitate certain biorelevant structures and facilitates successful escape from the immune system for more efficient accumulation in cancer cells, while "hard" inorganic part serves as a rigid and stable basis for the creation of cargo nanocarriers and imaging agents. This dissertation discusses the 5 critical points of safe biodegradable nanoplatforms, delivery of large biomolecules, and cytotoxicity regarding the shape of nanoparticles. As a result novel fluorescent biodegradable oxamide-based organosilica nanoparticles were developed, light-triggered surface charge reversal for large biomolecule delivery was applied with hollow bridged silsesquioxane nanomaterials, and biocompatibility of periodic mesoporous organosilicas with different morphologies was studied. Furthermore, the current achievements and future perspectives of mesoporous silica organosilica, and silsesquioxane nanoparticles were considered in regards to their biomedical applications and summarized in two reviews.