Source abstract
Abstract
Abstract Drug resistance is a major problem in cancer treatment. Herein, the design of a dual‐responsive Pt(IV)/Ru(II) bimetallic polymer (PolyPt/Ru) to treat cisplatin‐resistant tumors in a patient‐derived xenograft (PDX) model is reported. PolyPt/Ru is an amphiphilic ABA‐type triblock copolymer. The hydrophilic A blocks consist of biocompatible poly(ethylene glycol) (PEG). The hydrophobic B block contains reduction‐responsive Pt(IV) and red‐light‐responsive Ru(II) moieties. PolyPt/Ru self‐assembles into nanoparticles that are efficiently taken up by cisplatin‐resistant cancer cells. Irradiation of cancer cells containing PolyPt/Ru nanoparticles with red light generates 1O2, induces polymer degradation, and triggers the release of the Ru(II) anticancer agent. Meanwhile, the anticancer drug, cisplatin, is released in the intracellular environment via reduction of the Pt(IV) moieties. The released Ru(II) anticancer agent, cisplatin, and the generated 1O2 have different anticancer mechanisms; their synergistic effects inhibit the growth of drug‐resistant cancer cells. Furthermore, PolyPt/Ru nanoparticles inhibit tumor growth in a PDX mouse model because they circulate in the bloodstream, accumulate at tumor sites, exhibit good biocompatibility, and do not cause side effects. The results demonstrate that the development of stimuli‐responsive multi‐metallic polymers provides a new strategy to overcome drug resistance.
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Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Nanoplatforms for cancer theranostics · Metal complexes synthesis and properties
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Affiliations
CAS Key Laboratory of Soft Matter Chemistry Hefei National Laboratory for Physical Sciences at the Microscale Department of Polymer Science and Engineering University of Science and Technology of China Hefei 230026 China
Max Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 Germany
Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
University of Chinese Academy of Sciences Beijing 100049 China
State Key Laboratory of Fine Chemicals Dalian University of Technology 2 Linggong Road, Hi‐Tech Zone Dalian 116024 China
Funding
Recruitment Program of Global Experts · Deutsche Forschungsgemeinschaft · Natural Science Foundation of Anhui Province · National Natural Science Foundation of China · Chinese Academy of Sciences · National Basic Research Program of China
References (40)
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