Cu2+-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy

In this study, a pH-responsive controlled-release mesoporous silica nanoparticle (MSN) formulation was developed. The MSNs were functionalized with a histidine (His)-tagged targeting peptide (B3int) through an amide bond, and loaded with an anticancer drug (cisplatin (CP)) and a lysosomal destabilization mediator (chloroquine (CQ)). Cu2+ was then used to seal the pores of the MSNs via chelation with the His-tag. The resultant nanoparticles showed pH-responsive drug release, and could effectively target tumor cells via the targeting effect of B3int. The presence of CP and Cu2+ permits reactive oxygen species to be generated inside cells; thus, the chemotherapeutic effect of CP is augmented by chemodynamic therapy. In vitro and in vivo experiments showed that the nanoparticles are able to effectively kill tumor cells. An in vivo cancer model revealed that the nanoparticles increase apoptosis in tumor cells, and thereby diminish the tumor volume. No off-target toxicity was noted. It thus appears that the functionalized MSNs developed in this work have great potential for targeted, synergistic anticancer therapies.

Automated summary

In this study, pH-responsive mesoporous silica nanoparticles (MSN) were developed for targeted and synergistic anticancer therapy. The MSNs, functionalized with a histidine-tagged targeting peptide, showed pH-responsive drug release and effectively targeted tumor cells. The presence of an anticancer drug and Cu2+ enhanced the chemotherapeutic effect by generating reactive oxygen species. In vitro and in vivo experiments demonstrated the effective killing of tumor cells and diminished tumor volume without off-target toxicity. The functionalized MSNs show great potential for targeted and synergistic anticancer therapies.