Precisely size controlled drug-silica nanoconjugate for cancer therapy

silica;nanoparticle;nanoconjugate;cancer diagnosis and therapy;size effect;toxicity

Tang, Li

关键词: silica;    nanoparticle;    nanoconjugate;    cancer diagnosis and therapy;    size effect;    toxicity;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/34542/Tang_Li.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The goal of my Ph. D. research is to develop a precisely size-controlled drug conjugated silica nanoparticles as a new type of drug delivery system for improved cancer therapy. By using such monodisperse, drug-containing NPs with discrete and incremental difference in sizes, my aim is to study and elucidate the existing relationships among particle size, biologic processing, and therapeutic functionality and to identify the optimal size of nanomedicine for the highest anticancer efficacy. I developed a novel drug delivery platform based on drug-silica nanoconjugates (drug-NCs) that can be controllably fabricated with nearly any desired sizes between 20 and 200 nm, with extremely narrow particle size distribution (less than 10% coefficient of variation), and 10-20% drug loading and controlled drug release profile. These drug-NCs can be easily prepared on a gram scale also with perfectly controlled size and monodisperse size distribution. The in vitro and in vivo studies using these size-controlled drug-NCs demonstrated that particles of smaller sizes (≤50nm) are more efficient in bypassing the systemic, tissue, and cellular barriers, the three physiological barriers that are critical for effective drug delivery for cancer treatment. Interestingly, the drug-NC of 50 nm showed enhanced efficacy for inhibiting both primary tumor growth and tumor metastasis in breast cancer models in vivo. Further application of using the size controlled dual-modal silica NCs for targeted imaging of metastatic lymph nodes was studied. By demonstrating the long term safety in preliminary toxicology studies and addressing several formulation/development issues (e.g. salt-stability, scalability and lyophilizability, etc.), we developed a potentially clinically applicable, silica based drug-NCs with the optimized size for cancer therapy. My Ph.D. research not only established the design criteria of nanomedicine for cancer therapy, but also offered a solution to improve anticancer efficacy by precisely controlling the physicochemical properties of nanomedicine.