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Cu^{2+}-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy

Zhang, Yanyan; Lou, Jiadong; Williams, Gareth R; Ye, Yuhan; Ren, Dandan; Shi, Anhua; Wu, Junzi; ... Zhu, Li-Min; + view all (2022) Cu^{2+}-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy. Pharmaceutics , 14 (6) , Article 1200. 10.3390/pharmaceutics14061200. Green open access

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Abstract

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.

Type: Article
Title: Cu^{2+}-Chelating Mesoporous Silica Nanoparticles for Synergistic Chemotherapy/Chemodynamic Therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/pharmaceutics14061200
Publisher version: https://doi.org/10.3390/pharmaceutics14061200
Language: English
Additional information: © 2022 MDPI. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: mesoporous silica nanoparticles; chelation; gatekeeper; synergistic treatment
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10149956
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