Unsaturated nitrogen-rich polymer poly(L-histidine) gated reversibly switchable mesoporous silica nanoparticles using graft to strategy for drug controlled release

A novel and intelligent pH-controlled system having an on-off switch based on poly(t-histidine) (PLH) and poly(ethylene glycol) (PEG) coated mesoporous silica nanoparticles (MSNs) (MSNs-PLH-PEG) was designed and evaluated for tumor specific drug release. The unsaturated nitrogen-rich polymer, PLH, which can change its solubility at different pH values, was employed for establishing the reversible on-off switch. In vitro drug release results demonstrated that MSNs-PLH-PEG has a pH-controlled on-off profile with the change of pH value between pH 7.4 and 5.0. Furthermore, in vitro cellular uptake study results showed that the entrapped drug could be efficiently released from MSNs-PLH-PEG under acidic endosome/lysosome. In vitro cell cytotoxicity and in vivo antitumor studies results indicated that sorafenib loaded MSNs-PLH-PEG exhibited good anti-proliferation and tumor growth inhibition effects. Haemolysis assay and histological analysis of MSNs-PLH-PEG showed negligible haemolysis activity and no visible tissue toxicity at the test dose. This study represents a promising and intelligent pH controlled intelligent system for drug delivery and controlled release. Statement of Significance A novel pH-controlled intelligent and reversible on-off switch system based on poly(-histidine) and poly(ethylene glycol) coated mesoporous silica nanoparticles (MSNs-PLH-PEG) by graft to synthesis method was constructed for tumor specific drug release. The unsaturated nitrogen-rich pH-sensitive polymer, PLH, which can change its solubility in different pH values, was employed as the reversible on-off switch in MSNs for the first time. The pH-controlled on-off switch manner was observed in the drug release results in vitro. In the in vivo antitumor studies, sorafenib loaded MSNs-PLH-PEG could effectively suppressed tumor growth in H22 tumor bearing mice. It is expected that the pH-controlled intelligent on-off' switch system we designed holds remarkable promise and provides valuable strategy for possible applications in cancer therapy. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.