Cu<sup>2+</sup>-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy
Yanyan Zhang,
Jiadong Lou,
Gareth R. Williams,
Yuhan Ye,
Dandan Ren,
Anhua Shi,
Junzi Wu,
Wenling Chen,
Li-Min Zhu
Affiliations
Yanyan Zhang
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
Jiadong Lou
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
Gareth R. Williams
UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
Yuhan Ye
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
Dandan Ren
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
Anhua Shi
The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming 650500, China
Junzi Wu
The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming 650500, China
Wenling Chen
School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China
Li-Min Zhu
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
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.