Show simple item record

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

dc.contributor.author Simnick, Andrew J
dc.contributor.author Valencia, C Alexander
dc.contributor.author Liu, Rihe
dc.contributor.author Chilkoti, Ashutosh
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:27:05Z
dc.date.issued 2010-04-27
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20334355
dc.identifier.uri https://hdl.handle.net/10161/4103
dc.description.abstract 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.
dc.language eng
dc.language.iso en_US
dc.publisher American Chemical Society (ACS)
dc.relation.ispartof ACS Nano
dc.relation.isversionof 10.1021/nn901732h
dc.subject Elastin
dc.subject Humans
dc.subject Hydrophobic and Hydrophilic Interactions
dc.subject Integrin alphaVbeta3
dc.subject K562 Cells
dc.subject Ligands
dc.subject Micelles
dc.subject Nanoparticles
dc.subject Peptides
dc.subject Temperature
dc.title Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer.
dc.title.alternative
dc.type Journal article
duke.contributor.id Chilkoti, Ashutosh|0116676
dc.description.version Version of Record
duke.date.pubdate 2010-4-0
duke.description.issue 4
duke.description.volume 4
dc.relation.journal Acs Nano
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20334355
pubs.begin-page 2217
pubs.end-page 2227
pubs.issue 4
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Chemistry
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.organisational-group Trinity College of Arts & Sciences
pubs.publication-status Published
pubs.volume 4
dc.identifier.eissn 1936-086X


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record