Enzyme-Degradable Self-Assembled Nanostructures from Polymer鈥揚eptide Hybrids

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• 作者：Daniel Bacinello ; Elisabeth Garanger ; Daniel Taton ; Kam Chiu Tam ; S茅bastien Lecommandoux
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：May 12, 2014
• 年：2014
• 卷：15
• 期：5
• 页码：1882-1888
• 全文大小：379K
• 年卷期：v.15,no.5(May 12, 2014)
• ISSN：1526-4602

文摘

The peptide PVGLIG, which is known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to 伪-alkene poly(trimethylene carbonate) (PTMC) blocks of varying sizes via UV-initiated thiol-ene 鈥渃lick鈥?chemistry. The PTMC precursor was synthesized by metal-free ring-opening polymerization using allyl 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鈥搒hell, 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.