Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.

Autor:	Saha S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Banskota S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Liu J; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Zakharov N; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Dzuricky M; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Li X; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Fan P; Duke University School of Medicine, Department of Medicine Oncology and Duke Cancer Institute PK/PD Core Laboratory, Durham, North Carolina 27710, United States., Deshpande S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Spasojevic I; Duke University School of Medicine, Department of Medicine Oncology and Duke Cancer Institute PK/PD Core Laboratory, Durham, North Carolina 27710, United States., Sharma K; Molecular Microscopy Consortium, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, United States., Borgnia MJ; Molecular Microscopy Consortium, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, United States., Schaal JL; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Raman A; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Kim S; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Bhattacharyya J; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States., Chilkoti A; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, United States.
Jazyk:	angličtina
Zdroj:	Nano letters [Nano Lett] 2022 Jul 27; Vol. 22 (14), pp. 5898-5908. Date of Electronic Publication: 2022 Jul 15.
DOI:	10.1021/acs.nanolett.2c01850
Abstrakt:	The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation state in the same nanoparticle system that would allow its optimal design. To address this lacuna, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enables covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by ∼45-fold, but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.
Databáze:	MEDLINE
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