SYNTHESIS OF COBALAMIN-GRAFTED SILICA NANOPARTICLES FOR TARGETING CANCER CELLS

Abstract

Targeted therapy has been developed to reduce side effects of anticancer agents by specific localization of the drug to target only the cancer cells. In this thesis, a novel drug delivery system for targeting cancer cells was successfully synthesized. The system consisted of porous silica nanoparticle as the drug vehicle, cisplatin (CDDP) as the drug model, and cobalamin (Cbl) as the targeting molecule for cancer cells. Porous silica nanoparticle (PSNs, 1) were firstly prepared by sol-gel method, but the drug-loading capacity was only 7% as determined by ICP-AES. Thus, surface modification of PSNs with pendent carboxyl groups was carried out to obtain carboxyl-porous silica nanoparticles (PSNsCOOH, 2), of which the drug-loading capacity notably increased up to 59%. Then, the targeting molecule, [Cbl-CDDP]+ was grafted on CDDP@PSNsCOOH (3), resulting in CDDP@CblPSNsCOOH (4). The obtained particles were characterized by various techniques including XRD, IR, UV-vis, SEM and nanosizer. The particles (4) were spherical and monodisperse with an average diameter of 316 nm. To mimic biological reduction in cancer cells, drug release studies at pH 5.5 revealed that chemical reduction of (4) with NaBH4 gave [Co2+(Cbl)] and significantly induced release of the Pt drug. The results suggested that Cbl not only could serve as a targeting molecule but also a gatekeeper to prevent the drug release before reaching the targeted cells.