Enzyme-Degradable Self-Assembled Nanostructures from Polymer-Peptide Hybrids

Abstract : The peptide PVGLIG, which is known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to a-alkene poly(trimethylene carbonate) (PTMC) blocks of varying sizes via UV-initiated thiol-ene "click" chemistry. The PTMC precursor was synthesized by metal-free ring-opening polymerization using ally! alcohol as an initiator and an N-heterocyclic carbene as an organic catalyst. The unprecedented PVGLIG-b-PTMC hybrids were self-assembled in aqueous solution and various submicrometer-sized morphologies obtained by a nanoprecipitation process. Characterization of particle morphology was carried out by multiangle dynamic light scattering (DLS) and static light scattering (SLS) evidencing spherical nanoparticles with different morphologies and narrow size distributions. Microstructure details were also observed on transmission electron micrographs and were in good agreement with light scattering measurements showing the assembly of core shell, large compound micelles, and vesicle morphologies, the particle morphology varying with the hydrophilic weight fractions (f) of the hybrids. These nanostructures displayed selective degradation in the presence of the cancer-associated enzyme MMP-2, as probed by the morphological change both by TEM and DLS. All these results demonstrated that PVGLIG-b-PTMC hybrids were suitable to target the tumor microenvironment.
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Daniel Bacinello, Elisabeth Garanger, Daniel Taton, Kam Chiu Tam, Sébastien Lecommandoux. Enzyme-Degradable Self-Assembled Nanostructures from Polymer-Peptide Hybrids . Biomacromolecules, American Chemical Society, 2014, 15 (5), pp.1882-1888. ⟨10.1021/bm500296n ⟩. ⟨hal-01369962⟩



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