Albumin-gated zwitterion-stabilized mesoporous silica nanorod as a pH-responsive drug delivery system

Silica nanoparticles as drug delivery systems (DDS) have received huge attention in nanomedicine research. However, their drug release processes were usually discussed in the absence of proteins, which are abundant in real delivery media and likely to affect the release behaviors. In this work, novel pH-sensitive silica-based DDSs were constructed using the endogenous protein, human serum albumin (HSA), as the gatekeeper, and their release properties in protein-containing media were measured for the first time. As-synthesized mesoporous silica nanorod (MSNR) was modified with zwitterions to suppress the nonspecific adsorption of protein and to improve the dispersity. HSA was fixed onto MSNR through drug-protein interactions and covalent bonds, respectively. Benzoic-imine bonds were introduced into the designs to realize pH responsiveness. The fluorescence quenching effect of drugs on HSA was used to monitor the drug release in simulated body fluids containing proteins. The results indicated that protein gating could effectively reduce premature release in normal blood environment. The endogenous protein capping, high dispersity and stability, considerable loading content, low cytotoxicity and favorable responsiveness to acidic microenvironment enable the present structures to be promising carriers for chemotherapy drugs.