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Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake.

Publication ,  Journal Article
Macewan, SR; Chilkoti, A
Published in: Nano letters
June 2012

Cell-penetrating peptides (CPPs) are a class of molecules that enable efficient internalization of a wide variety of cargo in diverse cell types, making them desirable for delivery of anticancer drugs to solid tumors. For CPPs to be useful, it is important to be able to turn their function on in response to an external trigger that can be spatially localized in vivo. Here we describe an approach to turning on CPP function by modulation of the local density of arginine (Arg) residues by temperature-triggered micelle assembly of diblock copolymer elastin-like polypeptides (ELP(BC)s). A greater than 8-fold increase in cellular uptake occurs when Arg residues are presented on the corona of ELP(BC) micelles, as compared to the same ELP(BC) at a temperature in which it is a soluble unimer. This approach is the first to demonstrate digital 'off-on' control of CPP activity by an extrinsic thermal trigger in a clinically relevant temperature range by modulation of the interfacial density of Arg residues on the exterior of a nanoparticle.

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Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

June 2012

Volume

12

Issue

6

Start / End Page

3322 / 3328

Related Subject Headings

  • Protein Engineering
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Materials Testing
  • Humans
  • Cell Membrane
  • Arginine
 

Citation

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Macewan, S. R., & Chilkoti, A. (2012). Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake. Nano Letters, 12(6), 3322–3328. https://doi.org/10.1021/nl301529p
Macewan, Sarah R., and Ashutosh Chilkoti. “Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake.Nano Letters 12, no. 6 (June 2012): 3322–28. https://doi.org/10.1021/nl301529p.
Macewan, Sarah R., and Ashutosh Chilkoti. “Digital switching of local arginine density in a genetically encoded self-assembled polypeptide nanoparticle controls cellular uptake.Nano Letters, vol. 12, no. 6, June 2012, pp. 3322–28. Epmc, doi:10.1021/nl301529p.
Journal cover image

Published In

Nano letters

DOI

EISSN

1530-6992

ISSN

1530-6984

Publication Date

June 2012

Volume

12

Issue

6

Start / End Page

3322 / 3328

Related Subject Headings

  • Protein Engineering
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Materials Testing
  • Humans
  • Cell Membrane
  • Arginine