Fighting Against Cisplatin-Resistant Tumors Using Responsive Pt(IV)/Ru(II) Bimetallic Polymers
Final Report Abstract
Drug resistance is a major problem in cancer treatment. In this project, we designed a dual-responsive Pt(IV)/Ru(II) bimetallic polymer (PolyPt/Ru) to treat cisplatin-resistant tumors. We demonstrated its potential application in a patient-derived xenograft (PDX) model. 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 cisplatinresistant 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, the generated 1O2 have different anticancer mechanisms. Their synergistic effects inhibit the growth of drug-resistant cancer cells. Furthermore, PolyPt/Ru nanoparticles inhibited tumor growth in a PDX mouse model because they circulate in the blood stream, accumulate at tumor sites, exhibit good biocompatibility, and does not cause side effects. Our results demonstrate that the development of stimuli-responsive multi-metallic polymers provides a new strategy to overcome drug resistance.
Publications
- Reconfiguring surface functions using visible-light-controlled metal-ligand coordination. Nat. Commun. 2018, 9, 3842
Xie, C.; Sun, W.; Lu, H.; Kretzschmann, A.; Liu, J.; Wagner, M.; Butt, H. J.; Deng, X.; Wu, S.
(See online at https://doi.org/10.1038/s41467-018-06180-7) - Red-Light-Controlled Release of Drug-Ru Complex Conjugates from Metallopolymer Micelles for Phototherapy in Hypoxic Tumor Environments. Adv. Funct. Mater. 2018, 28, 1804227
Sun, W.; Wen, Y.; Thiramanas, R.; Chen, M.; Han, J.; Gong, N.; Wagner, M.; Jiang, S.; Meijer, M. S.; Bonnet, S.; Butt, H.-J.; Mailänder, V.; Liang, X.-J.; Wu, S.
(See online at https://doi.org/10.1002/adfm.201804227) - Fighting against Drug-Resistant Tumors using a Dual-Responsive Pt(IV)/Ru(II) Bimetallic Polymer. Adv. Mater. 2020, 32, 2004766
Zeng, X.; Wang, Y.; Han, J.; Sun, W.; Butt, H. J.; Liang, X. J.; Wu, S.
(See online at https://doi.org/10.1002/adma.202004766) - Fighting against drug-resistant tumors using a dual-responsive Pt(IV)/Ru(II) bimetallic polymer. Advanced Materials 2020, 2004766
Zeng, X.L., Y.F. Wang, J.X. Han, W. Sun, H.-J. Butt, X.-J. Liang & S. Wu
(See online at https://doi.org/10.1002/adma.202004766) - Long alkyl side chains simultaneously improve mechanical robustness and healing ability of a photoswitchable polymer. Macromolecules 2020, 53, 8562-8569
Zhang, Z., M. Chen, I. Schneider, Y. Liu, S. Liang, S. Sun, K. Koynov, H.-J. Butt & Si Wu
(See online at https://doi.org/10.1021/acs.macromol.0c01784) - Metallopolymer Organohydrogels with Photo-Controlled Coordination Crosslinks Work Properly Below 0 ℃. Adv. Mater. 2020, 32, 1908324
Liu, J.; Xie, C.; Kretzschmann, A.; Koynov, K.; Butt, H. J.; Wu, S.
(See online at https://doi.org/10.1002/adma.201908324) - Nanostructured polymer assemblies stabilize photoactivatable anticancer ruthenium complexes under physiological conditions. J. Inorg. Biochem. 2020, 207, 111052
Chen, M.; Sun, W.; Kretzschmann, A.; Butt, H.-J.; Wu, S.
(See online at https://doi.org/10.1016/j.jinorgbio.2020.111052) - Ru–Se Coordination: A New Dynamic Bond for Visible-Light- Responsive Materials. J. Am. Chem. Soc. 2021, 143, 12736-12744
Han, J.; Xie, C.; Huang, Y.-S.; Wagner, M.; Liu, W.; Zeng, X.; Liu, J.; Sun, S.; Koynov, K.; Butt, H.-J.; Wu, S.
(See online at https://doi.org/10.1021/jacs.1c05648)
