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Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug.

Publication ,  Journal Article
Costa, SA; Mozhdehi, D; Dzuricky, MJ; Isaacs, FJ; Brustad, EM; Chilkoti, A
Published in: Nano letters
January 2019

Polypeptides are promising carriers for chemotherapeutics: they have minimal toxicity, can be recombinantly synthesized with precise control over molecular weight, and enhance drug pharmacokinetics as self-assembled nanoparticles. Polypeptide-based systems also provide the ability to achieve active targeting with genetically encoded targeting ligands. While passive targeting promotes accumulation of nanocarriers in solid tumors, active targeting provides an additional layer of tunable control and widens the therapeutic window. However, fusion of most targeting proteins to polypeptide carriers exposes the limitations of this approach: the residues that are used for drug attachment are also promiscuously distributed on protein surfaces. We present here a universal methodology to solve this problem by the site-specific attachment of extrinsic moieties to polypeptide drug delivery systems without cross-reactivity to fused targeting domains. We incorporate an unnatural amino acid, p-acetylphenylalanine, to provide a biorthogonal ketone for attachment of doxorubicin in the presence of reactive amino acids in a nanobody-targeted, elastin-like polypeptide nanoparticle. These nanoparticles exhibit significantly greater cytotoxicity than nontargeted controls in multiple cancer cell lines.

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Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

January 2019

Volume

19

Issue

1

Start / End Page

247 / 254

Related Subject Headings

  • Phenylalanine
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • Humans
  • Elastin
  • Drug Delivery Systems
 

Citation

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Costa, S. A., Mozhdehi, D., Dzuricky, M. J., Isaacs, F. J., Brustad, E. M., & Chilkoti, A. (2019). Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug. Nano Letters, 19(1), 247–254. https://doi.org/10.1021/acs.nanolett.8b03837
Costa, Simone A., Davoud Mozhdehi, Michael J. Dzuricky, Farren J. Isaacs, Eric M. Brustad, and Ashutosh Chilkoti. “Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug.Nano Letters 19, no. 1 (January 2019): 247–54. https://doi.org/10.1021/acs.nanolett.8b03837.
Costa SA, Mozhdehi D, Dzuricky MJ, Isaacs FJ, Brustad EM, Chilkoti A. Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug. Nano letters. 2019 Jan;19(1):247–54.
Costa, Simone A., et al. “Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug.Nano Letters, vol. 19, no. 1, Jan. 2019, pp. 247–54. Epmc, doi:10.1021/acs.nanolett.8b03837.
Costa SA, Mozhdehi D, Dzuricky MJ, Isaacs FJ, Brustad EM, Chilkoti A. Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug. Nano letters. 2019 Jan;19(1):247–254.
Journal cover image

Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

January 2019

Volume

19

Issue

1

Start / End Page

247 / 254

Related Subject Headings

  • Phenylalanine
  • Peptides
  • Neoplasms
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • Humans
  • Elastin
  • Drug Delivery Systems