Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.

Journal Article (Journal Article)

Valency is a fundamental principle to control macromolecular interactions and is used to target specific cell types by multivalent ligand-receptor interactions using self-assembled nanoparticle carriers. At the concentrations encountered in solid tumors upon systemic administration, these nanoparticles are, however, likely to show critical micelle concentration (CMC)-dependent disassembly and thus loss of function. To overcome this limitation, core-crosslinkable micelles of genetically encoded resilin-/elastin-like diblock polypeptides were recombinantly synthesized. The amphiphilic constructs were covalently photo-crosslinked through the genetically encoded unnatural amino acid para -azidophenylalanine in their hydrophobic block and they carried different anticancer ligands on their hydrophilic block: the wild-type tenth human fibronectin type III domain, a GRGDSPAS peptide-both targeting αv β3 integrin-and an engineered variant of the third fibronectin type III domain of tenascin C that is a death receptor 5 agonist. Although uncrosslinked micelles lost most of their targeting ability below their CMC, the crosslinked analogues remained active at concentrations up to 1000-fold lower than the CMC, with binding affinities that are comparable to antibodies.

Full Text

Duke Authors

Cited Authors

  • Weber, P; Dzuricky, M; Min, J; Jenkins, I; Chilkoti, A

Published Date

  • October 2021

Published In

Volume / Issue

  • 22 / 10

Start / End Page

  • 4347 - 4356

PubMed ID

  • 34477380

Pubmed Central ID

  • PMC9339257

Electronic International Standard Serial Number (EISSN)

  • 1526-4602

International Standard Serial Number (ISSN)

  • 1525-7797

Digital Object Identifier (DOI)

  • 10.1021/acs.biomac.1c00897


  • eng