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Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models.

Publication ,  Journal Article
Banskota, S; Saha, S; Bhattacharya, J; Kirmani, N; Yousefpour, P; Dzuricky, M; Zakharov, N; Li, X; Spasojevic, I; Young, K; Chilkoti, A
Published in: Nano Lett
April 8, 2020

Small-molecule therapeutics demonstrate suboptimal pharmacokinetics and bioavailability due to their hydrophobicity and size. One way to overcome these limitations-and improve their efficacy-is to use "stealth" macromolecular carriers that evade uptake by the reticuloendothelial system. Although unstructured polypeptides are of increasing interest as macromolecular drug carriers, current recombinant polypeptides in the clinical pipeline typically lack stealth properties. We address this challenge by developing new unstructured polypeptides, called zwitterionic polypeptides (ZIPPs), that exhibit "stealth" behavior in vivo. We show that conjugating paclitaxel to a ZIPP imparts amphiphilicity to the polypeptide chain that is sufficient to drive its self-assembly into micelles. This in turn increases the half-life of paclitaxel by 17-fold compared to free paclitaxel, and by 1.6-fold compared to the nonstealth control, i.e., ELP-paclitaxel. Treatment of mice bearing highly aggressive prostate or colon cancer with a single dose of ZIPP-paclitaxel nanoparticles leads to near-complete eradication of the tumor, and these nanoparticles have a wider therapeutic window than Abraxane, an FDA-approved taxane nanoformulation.

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Published In

Nano Lett

DOI

EISSN

1530-6992

Publication Date

April 8, 2020

Volume

20

Issue

4

Start / End Page

2396 / 2409

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Peptides
  • Paclitaxel
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoconjugates
  • Mice, Nude
  • Mice
  • Humans
  • Cell Line, Tumor
 

Citation

APA
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ICMJE
MLA
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Banskota, S., Saha, S., Bhattacharya, J., Kirmani, N., Yousefpour, P., Dzuricky, M., … Chilkoti, A. (2020). Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models. Nano Lett, 20(4), 2396–2409. https://doi.org/10.1021/acs.nanolett.9b05094
Banskota, Samagya, Soumen Saha, Jayanta Bhattacharya, Nadia Kirmani, Parisa Yousefpour, Michael Dzuricky, Nikita Zakharov, et al. “Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models.Nano Lett 20, no. 4 (April 8, 2020): 2396–2409. https://doi.org/10.1021/acs.nanolett.9b05094.
Banskota S, Saha S, Bhattacharya J, Kirmani N, Yousefpour P, Dzuricky M, et al. Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models. Nano Lett. 2020 Apr 8;20(4):2396–409.
Banskota, Samagya, et al. “Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models.Nano Lett, vol. 20, no. 4, Apr. 2020, pp. 2396–409. Pubmed, doi:10.1021/acs.nanolett.9b05094.
Banskota S, Saha S, Bhattacharya J, Kirmani N, Yousefpour P, Dzuricky M, Zakharov N, Li X, Spasojevic I, Young K, Chilkoti A. Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models. Nano Lett. 2020 Apr 8;20(4):2396–2409.
Journal cover image

Published In

Nano Lett

DOI

EISSN

1530-6992

Publication Date

April 8, 2020

Volume

20

Issue

4

Start / End Page

2396 / 2409

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Peptides
  • Paclitaxel
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoconjugates
  • Mice, Nude
  • Mice
  • Humans
  • Cell Line, Tumor