Facile synthesis of organosilica-capped mesoporous silica nanocarriers with selective redox-triggered drug release properties for safe tumor chemotherapy
Luying Shen, Shan Pan, Dechao Niu, Jianping He, Xiaobo Jia, Jina Hao, Jinlou Gu, Wenru Zhao, Pei Li and Yongsheng Li
As drug-delivery carriers for cancer chemotherapy, gatekeeper-capped mesoporous silica nanoparticles (MSNs) have been widely studied due to their high drug-loading capability, controlled drug release property and good biocompatibility. However, the currently reported gatekeeper-capped MSNs suffer from complex synthetic procedures, potential toxicity of gatekeepers, unsatisfactory control on drug stimuli-release, etc. In this work, we develop a simple but efficient approach to fabricate PEGylated organosilica-capped mesoporous silica nanoparticles (POMSNs) by employing a disulfide-doped organosilica coating as the gatekeeper formed by the hydrolysis and condensation of a silane coupling agent 3-(mercaptopropyl)trimethoxysilane (MPTMS) to block the mesopores of MSNs. Owing to the glutathione (GSH)-responsive biodegradation behavior of the disulfide-doped organosilica gatekeeper, the DOX-loaded POMSNs exhibit only 20% cell viability towards SMMC-7721 tumor cells, and almost no toxicity towards L-02 cells at a DOX concentration of 50 μg mL−1 was measured, demonstrating their selective cytotoxicity in vitro. More importantly, it is demonstrated that the DOX-loaded POMSNs exhibit a tumor inhibition rate of 71.3% and negligible systematic toxicity. Consequently, the resultant POMSNs show great potential as drug nanocarriers for redox-responsive drug release and passive-targeting tumor chemotherapy.