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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.

Publication ,  Journal Article
Saha, S; Banskota, S; Liu, J; Zakharov, N; Dzuricky, M; Li, X; Fan, P; Deshpande, S; Spasojevic, I; Sharma, K; Borgnia, MJ; Schaal, JL ...
Published in: Nano Lett
July 27, 2022

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.

Duke Scholars

Published In

Nano Lett

DOI

EISSN

1530-6992

Publication Date

July 27, 2022

Volume

22

Issue

14

Start / End Page

5898 / 5908

Location

United States

Related Subject Headings

  • Prodrugs
  • Platinum
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Cisplatin
  • Cell Line, Tumor
  • Antineoplastic Agents
 

Citation

APA
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MLA
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Saha, S., Banskota, S., Liu, J., Zakharov, N., Dzuricky, M., Li, X., … Chilkoti, A. (2022). 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. Nano Lett, 22(14), 5898–5908. https://doi.org/10.1021/acs.nanolett.2c01850
Saha, Soumen, Samagya Banskota, Jianqiao Liu, Nikita Zakharov, Michael Dzuricky, Xinghai Li, Ping Fan, et al. “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.Nano Lett 22, no. 14 (July 27, 2022): 5898–5908. https://doi.org/10.1021/acs.nanolett.2c01850.
Saha, Soumen, et al. “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.Nano Lett, vol. 22, no. 14, July 2022, pp. 5898–908. Pubmed, doi:10.1021/acs.nanolett.2c01850.
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. 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. Nano Lett. 2022 Jul 27;22(14):5898–5908.
Journal cover image

Published In

Nano Lett

DOI

EISSN

1530-6992

Publication Date

July 27, 2022

Volume

22

Issue

14

Start / End Page

5898 / 5908

Location

United States

Related Subject Headings

  • Prodrugs
  • Platinum
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice
  • Cisplatin
  • Cell Line, Tumor
  • Antineoplastic Agents