A platinum@polymer-catechol nanobraker enables radio-immunotherapy for crippling melanoma tumorigenesis, angiogenesis, and radioresistance.

Autor:	Li W; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Yan J; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Tian H; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Li B; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Wang G; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Sang W; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Zhang Z; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Zhang X; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China., Dai Y; Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.; MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China.
Jazyk:	angličtina
Zdroj:	Bioactive materials [Bioact Mater] 2022 Sep 24; Vol. 22, pp. 34-46. Date of Electronic Publication: 2022 Sep 24 (Print Publication: 2023).
DOI:	10.1016/j.bioactmat.2022.09.006
Abstrakt:	Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis, angiogenesis, and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression. Interdicting melanoma intrinsic growth signals, including the blockade of PD-L1 and mTOR signaling concurrently, cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance. Thence, we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody (aPD-L1) for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication. The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1: PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling; corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis, respectively. Further, high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy. Hereto, the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy. Such an ingenious tactic may provide substantial benefits to clinical melanoma patients. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Authors.)
Databáze:	MEDLINE
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