Development of Multifunctional Silica Nanoparticles as Cancer Targeting Theranostics

Abstract

Cancer, claiming 10 million lives annually, demands targeted therapies to mitigate chemotherapy's impact on healthy cells. Silica nanoparticles (SiNPs) as drug carriers excel in nanomedicine due to their structural advantages. SiNPs, easily modified, offer controlled drug release by introducing functional groups for cancer cell targeting. Incorporating imaging agents enables simultaneous diagnostics and therapeutics, known as theranostics. In this study, we designed and synthesized a multifunctional linker that can conjugate folic acid (FA), a targeting ligand and camptothecin (CPT), an anticancer drug. A multifunctional bismethallyl silane linker that can be effectively grafted on the surface of SiNPs was prepared according to the synthesis method reported in the previousl research. At the end of this linker, cyclopropene and maleimide were introduced and they were able to allow the targeting ligand and therapeutic drug to be conjugated, respectively. Folic acid conjugated tetrazine and CPT-thiol group were incorporated into SiNP through bioorthgonal reactions. Accordingly, this functionalized SiNPs exhibited good cytotoxicity against cancer cells due to high cellular uptake and GSH-responsive drug release. In order to to enhance the efficacy of anti-cancer activity, a stimuli-responsive drug delivery system on the basis of a novel linker having a disulfide self-degradable spacer was devised. A linear or cyclic disulfide was synthesized and used as a key fragment for the synthesis of stimuli-responsive multifunctional linkers. Further studies on the conjugation of stimuli-responsive linkers with SiNPs are currently in progress.