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.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Saha, S; Banskota, S; Liu, J; Zakharov, N; Dzuricky, M; Li, X; Fan, P; Deshpande, S; Spasojevic, I; Sharma, K; Borgnia, MJ; Schaal, JL; Raman, A; Kim, S; Bhattacharyya, J; Chilkoti, A

Published Date

  • July 2022

Published In

Volume / Issue

  • 22 / 14

Start / End Page

  • 5898 - 5908

PubMed ID

  • 35839459

Electronic International Standard Serial Number (EISSN)

  • 1530-6992

International Standard Serial Number (ISSN)

  • 1530-6984

Digital Object Identifier (DOI)

  • 10.1021/acs.nanolett.2c01850

Language

  • eng