Novel Thioacetal-Bridged Hollow Mesoporous Organosilica Nanoparticles with ROS-Responsive Biodegradability for Smart Drug Delivery

摘要

Intelligent, efficient silica nanoparticles for drug delivery system in cancer therapy have a great application potential, but the biodegradability of silica nanoparticles becomes an intractable hindrance. In this work, novel reactive oxygen species (ROS)-responsive hollow mesoporous organosilica nanoparticles (HMONs) coated with polydopamine (PDA) biofilm and amino-terminated methoxy poly(ethylene glycol) (mPEG-NH2) were synthesized and applied in the smart drug delivery system (HMONs@PDA-mPEG) for the delivery of doxorubicin (DOX). The nanostructures and morphologies of nanoparticles were characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), N-2 adsorption/desorption, dynamic light scattering (DLS) and thermogravimetric analysis. Based on the "chemical homology" mechanism, physiologically active thioacetal-bridged silsesquioxane was molecularly incorporated into the framework of silica nanoparticles to form ROS-responsive HMONs, which was verified by the in vitro degradation experiment. The in vitro drug release profiles showed a synergistically pH-dependent and ROS-responsive drug release effect. MTT assay toward A549 cells demonstrated that drug carriers had a biocompatibility, and DOX-loaded nanoparticles (DNs) presented a concentration-dependent and time-dependent cell growth inhibition effect. In summary, the novel ROS-responsive HMONs@PDA-mPEG had a promising application as a smart drug delivery system in biomedical field.