Controlled release of DOX mediated by glutathione and pH dual-responsive hollow mesoporous silicon coated with polydopamine graft poly(poly(ethylene glycol) methacrylate) nanoparticles for cancer therapy

Abstract

The development of multifunctional nano-drug carriers has become one of the most effective and prevailing approaches to overcome the non-selectivity and low cell uptake efficiency of drugs, as well as various side effects of traditional chemotherapy drugs. Herein, we reported novel hollow mesoporous silica nanoparticles (HMSNs) coated with polydopamine (PDA) and poly(poly(ethylene glycol) methacrylate) (PPEGMA) (HMSNs@PDA-s-s-PPEGMA) for the treatment of cancer. The HMSNs mainly served as a warehouse loading anticancer drug doxorubicin (DOX); the covering of PDA acted as pH-sensitive gatekeepers to control the diffusion and/or release of DOX from HMSNs in different pH stimuli environments, whilst the grafting of PPEGMA on the surface of HMSNs@PDA by disulfide bonds and atom transfer radical polymerization (ATRP) increased the stability under physiological conditions and showed reductant sensitive responsiveness. The HMSNs@PDA-s-s-PPEGMA had a high loading capacity and entrapment efficiency of drugs through loading twice but low cytotoxicity. The in vitro release results indicated that the HMSNs@PDA-s-s-PPEGMA exhibited a high sensitivity to pH and glutathione (GSH) due to the PDA coating and disulfide bonds, which could control DOX release as intelligent "switches". The drug-loaded formulations could better be taken up by the cells, formed a higher concentration of DOX in the cells, and produced more remarkable apoptosis, thus achieving better treatment of tumors with high therapy efficacy. Therefore, the developed multifunctional materials could be used as a promising nano-drug carrier for cancer treatment.