Abstract
!""# # Abstract Unlike the traditional dose-dumping pharmaceutical preparations, nano-DDS (drug delivery system) with enhanced surface area not only are capable of transmitting hydrophobic drugs in vitro and in vivo with improved drug bioavailability/absorption, but also help to reduce dosage/side effects of drug. Mesoporous Silica Nanoparticles (MSNs) are known for its versatile advantages such as higher surface area, larger pore volume, tunable pore size and lower cytotoxicity. In this study, the gold nanoparticle (AuNP)-capped, amino-functionalized mesoporous silica nanoparticles (GCMSN) were fabricated as drug carriers, in which AuNPs were modified onto the MSNs via a weak gold-nitrogen bonding (6 kcal/mol) acting as gatekeeper. It was found in this study that, after cellular uptake of GCMSNs, the AuNPs were desorbed from MSNs due to the presence of a relatively higher concentration of intracellular glutathione (GSH, 10 mM), leading to the substitution of gold-thiol bonding (bonding affinity: 47 kcal/mol) for the former weak gold-nitrogen bonding. Such design enables the triggering of drug release from the nanocarriers without external energy (i.e., light/heat, electricity, or acoustic energy). The characterization of GCMSNs was investigated by Scanning/Transmission Electron Microscopy, Dynamic Light Scattering spectrometry, Zeta potential analyzer, UV-Vis/Fluorescence spectrometry, confocal microscopy, and powder X-ray diffraction analysis. In vitro studies show that our GCMSNs themselves were able to induce the oxidative stress in cancer cells, leading to higher cell death rate. Moreover, a hydrophobic anticancer drug (camptothecin, CPT) was encapsulated in the pore channels of GCMSNs, and the feasibility of practical drug delivery application was demonstrated in vitro . The controlled release of the anticancer drug shows excellent capability of killing human lung epithelial A549 cells . We thus concluded that Au-capped CPT-loaded MSNs not merely has the ability of controlling drug release, but also produces synergistic effect in treating cancer cells with less side effects and higher efficacy, which makes them a highly promising candidate as a new-generation nano-DDS carriers.