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Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.

Publication ,  Journal Article
Simnick, AJ; Valencia, CA; Liu, R; Chilkoti, A
Published in: ACS nano
April 2010

Multivalency is the increase in avidity resulting from the simultaneous interaction of multiple ligands with multiple receptors. This phenomenon, seen in antibody-antigen and virus-cell membrane interactions, is useful in designing bioinspired materials for targeted delivery of drugs or imaging agents. While increased avidity offered by multivalent targeting is attractive, it can also promote nonspecific receptor interaction in nontarget tissues, reducing the effectiveness of multivalent targeting. Here, we present a thermal targeting strategy--dynamic affinity modulation (DAM)--using elastin-like polypeptide diblock copolymers (ELP(BC)s) that self-assemble from a low-affinity to high-avidity state by a tunable thermal "switch", thereby restricting activity to the desired site of action. We used an in vitro cell binding assay to investigate the effect of the thermally triggered self-assembly of these ELP(BC)s on their receptor-mediated binding and cellular uptake. The data presented herein show that (1) ligand presentation does not disrupt ELP(BC) self-assembly; (2) both multivalent ligand presentation and upregulated receptor expression are needed for receptor-mediated interaction; (3) increased size of the hydrophobic segment of the block copolymer promotes multivalent interaction with membrane receptors, potentially due to changes in the nanoscale architecture of the micelle; and (4) nanoscale presentation of the ligand is important, as presentation of the ligand by micrometer-sized aggregates of an ELP showed a low level of binding/uptake by receptor-positive cells compared to its presentation on the corona of a micelle. These data validate the concept of thermally triggered DAM and provide rational design parameters for future applications of this technology for targeted drug delivery.

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Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

April 2010

Volume

4

Issue

4

Start / End Page

2217 / 2227

Related Subject Headings

  • Temperature
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • K562 Cells
  • Integrin alphaVbeta3
  • Hydrophobic and Hydrophilic Interactions
  • Humans
 

Citation

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Simnick, A. J., Valencia, C. A., Liu, R., & Chilkoti, A. (2010). Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer. ACS Nano, 4(4), 2217–2227. https://doi.org/10.1021/nn901732h
Simnick, Andrew J., C Alexander Valencia, Rihe Liu, and Ashutosh Chilkoti. “Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.ACS Nano 4, no. 4 (April 2010): 2217–27. https://doi.org/10.1021/nn901732h.
Simnick, Andrew J., et al. “Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.ACS Nano, vol. 4, no. 4, Apr. 2010, pp. 2217–27. Epmc, doi:10.1021/nn901732h.
Journal cover image

Published In

ACS nano

DOI

EISSN

1936-086X

ISSN

1936-0851

Publication Date

April 2010

Volume

4

Issue

4

Start / End Page

2217 / 2227

Related Subject Headings

  • Temperature
  • Peptides
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Micelles
  • Ligands
  • K562 Cells
  • Integrin alphaVbeta3
  • Hydrophobic and Hydrophilic Interactions
  • Humans