A pH-responsive polymer/mesoporous silica nano-container linked through an acid cleavable linker for intracellular controlled release and tumor therapy in vivo.

This paper proposes a pH-responsive polymer/mesoporous silica nano-container linked through an acid cleavable linker for intracellular controlled release and tumor therapy in vivo. In this system, the poly(acrylic acid) homopolymer (PAA), as a nanoscopic cap, is grafted onto the MSN through an acid cleavable linker (PAA-ACL-MSN). Doxorubicin (DOX), as a model drug, is used to assess the drug release behaviors and tumor therapy. At neutral pH, the linker is intact, resulting in blockage of pores and package of DOX. By the degradation of the linker at acidic pH, the grafted PAA is removed, which gives rise to uncapping and the subsequent pH-responsive controlled release of DOX. In vitro studies using a nasopharyngeal carcinoma cell line (HNE-1) prove that DOX loaded PAA-ACL-MSN (DOX@PAA-ACL-MSN) is endocytosed and demonstrates efficient operation at lysosomal pH, leading to significant cytotoxicity. As a preliminary tumor therapy in vivo, the progressive tumor development and inhibition following DOX@PAA-ACL-MSN treatment is monitored using bioluminescence imaging. By the examination of cell proliferation in tumor tissues and the comparison of body weight, it is revealed that the DOX@PAA-ACL-MSN is superior to free DOX in terms of therapeutic efficacy and side effects due to the enhanced permeability and retention effects and lower pH in tumor areas. We believe that this developed MSN based delivery system will provide a promising nanodevice for tumor therapy.