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Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles.

Publication ,  Journal Article
Wang, J; Saha, S; Schaal, JL; Yousefpour, P; Li, X; Chilkoti, A
Published in: Nano letters
November 2019

Bioactive peptides describe a very large group of compounds with diverse functions and wide applications, and their multivalent display by nanoparticles can maximize their activities. However, the lack of a universal nanoparticle platform and design rules for their optimal presentation limits the development and application of peptide ligand-decorated nanoparticles. To address this need, we developed a multivalent nanoparticle platform to study the impact of nanoparticle surface hydrophilicity and charge on peptide targeting and internalization by tumor cells. This system consists of micelles of a recombinant elastin-like polypeptide diblock copolymer (ELPBC) that present genetically encoded peptides at the micelle surface without perturbing the size, shape, stability, or peptide valency of the micelle, regardless of the peptide type. We created the largest extant set of 98 combinations of 15 tumor-homing peptides that are presented on the corona of this ELPBC micelle via 8 different peptide linkers that vary in their length and charge and also created control micelles that present the linker only. Analysis of the structure-function relationship of tumor cell targeting by this set of peptide-decorated nanoparticles enabled us to derive heuristics to optimize the delivery of peptides based on their physicochemical properties and to identify a peptide that is likely to be a widely useful ligand for targeting across nanoparticle types. This study shows that ELPBC micelles are a robust and convenient system for the presentation of diverse peptides and provides useful insights into the appropriate presentation of structurally diverse peptide ligands on nanoparticles based on their physicochemical properties.

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Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

November 2019

Volume

19

Issue

11

Start / End Page

7977 / 7987

Related Subject Headings

  • Recombinant Proteins
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Humans
  • Heuristics
 

Citation

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ICMJE
MLA
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Wang, J., Saha, S., Schaal, J. L., Yousefpour, P., Li, X., & Chilkoti, A. (2019). Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles. Nano Letters, 19(11), 7977–7987. https://doi.org/10.1021/acs.nanolett.9b03141
Wang, Jing, Soumen Saha, Jeffrey L. Schaal, Parisa Yousefpour, Xinghai Li, and Ashutosh Chilkoti. “Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles.Nano Letters 19, no. 11 (November 2019): 7977–87. https://doi.org/10.1021/acs.nanolett.9b03141.
Wang J, Saha S, Schaal JL, Yousefpour P, Li X, Chilkoti A. Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles. Nano letters. 2019 Nov;19(11):7977–87.
Wang, Jing, et al. “Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles.Nano Letters, vol. 19, no. 11, Nov. 2019, pp. 7977–87. Epmc, doi:10.1021/acs.nanolett.9b03141.
Wang J, Saha S, Schaal JL, Yousefpour P, Li X, Chilkoti A. Heuristics for the Optimal Presentation of Bioactive Peptides on Polypeptide Micelles. Nano letters. 2019 Nov;19(11):7977–7987.
Journal cover image

Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

November 2019

Volume

19

Issue

11

Start / End Page

7977 / 7987

Related Subject Headings

  • Recombinant Proteins
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Humans
  • Heuristics