Concentration Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles
| Autor: | Junseon Min, Ashutosh Chilkoti, Michael Dzuricky, Patrick Weber, Irene C Jenkins |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Polymers and Plastics biology Chemistry Tenascin C Bioengineering macromolecular substances Fibronectin type III domain Micelle Article Amino acid Elastin Biomaterials Critical micelle concentration Neoplasms Amphiphile Materials Chemistry biology.protein Biophysics Humans Insect Proteins Resilin Peptides Micelles |
| Zdroj: | Biomacromolecules |
| Popis: | 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 photocrosslinked 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 10(th) human fibronectin type III domain, a GRGDSPAS peptide — both targeting α(v)β(3) integrin — and an engineered variant of the 3(rd) fibronectin type III domain of tenascin C that is a death receptor 5 agonist. Whereas uncrosslinked micelles lost most of their targeting ability below their CMC, the crosslinked analogs remained active at concentrations up to 1000-fold lower than the CMC, with binding affinities that are comparable to antibodies. |
| Databáze: | OpenAIRE |
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