Targeted drug delivery system based on NIR-responsive nanoparticles

Abstract

Cancer is currently a fatal disease that affects many people, yet its treatment methods face significant limitations. A notable challenge pertains to the adverse effects of chemotherapy drugs, which many patients endure, further underscoring the necessity for effective drug delivery strategies. In this context, nanoparticles have emerged as a particularly promising solution, and a substantial body of research has been dedicated to investigating their potential as drug delivery carriers. Nonetheless, challenges persist, including the efficiency of drug delivery and the potential for adverse effects. To address these issues, this study developed a system designed to selectively target cancer cells with drugs, activated by specific stimuli. Chapter 2 presents a dual-stimuli-responsive drug delivery system that has been developed for the effective release of drugs within the tumor microenvironment and under NIR conditions. The system utilizes MS@GNR, a mesoporous silica-coated gold nanorod, which enables drug release through porous silica when heated by NIR. To mitigate the risk of drug leakage arising from the porous structure, the system is coated with PEG-PDS, which responds to GSH, a molecule overexpressed in cancer cells. This multifaceted approach offers a highly efficient targeting strategy, enabling precise drug release triggered by both GSH and NIR stimuli. Chapter 3 introduces a tumor-specific targeting system activated by NIR, designed to minimize general cell accumulation of antibody adapted DDS system while enhancing cancer cell targeting. The antibody adapted DDS system is engineered to regulate antigen-binding capacity by temperature. By utilizing the characteristic of antibodies losing binding to antigens at high temperatures, a system was applied in which antibody-antigen binding complexes are created and dissociation occurs at high temperatures. To build this system, a polymer that increases thermal stability was applied to the antibody. Thermal stabilization polymer coating prevents denaturation and restores binding ability, allowing heat to regulate binding. The system links thermal stabilized EGFR antibody to gold nanorods (GNRs), with antigens loaded onto the system. Upon NIR irradiation, the system releases antigens around tumors, inducing immune activation and targeting cancer cells with high precision, thereby reducing off-target effects and enhancing therapeutic efficiency.