Université de Bordeaux , LCPO, UMR 5629, F-33600 Pessac, France.
Biomacromolecules. 2014 May 12;15(5):1882-8. doi: 10.1021/bm500296n. Epub 2014 Apr 10.
The peptide PVGLIG, which is known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to α-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 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-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.
肽 PVGLIG 已知可被肿瘤相关酶基质金属蛋白酶-2（MMP-2）选择性切割，通过紫外光引发的硫醇-烯“点击”化学将其连接到不同大小的α-烯烃聚（三亚甲基碳酸酯）（PTMC）块上。PTMC 前体通过无金属开环聚合使用烯丙醇作为引发剂和氮杂环卡宾作为有机催化剂合成。PTMC 前体通过无金属开环聚合使用烯丙醇作为引发剂和氮杂环卡宾作为有机催化剂合成。在水溶液中自组装，通过纳米沉淀工艺得到各种亚微米级形貌。通过多角度动态光散射（DLS）和静态光散射（SLS）对粒子形貌进行了表征，证明了具有不同形貌和窄粒径分布的球形纳米粒子。在透射电子显微镜上也观察到了微观结构细节，与光散射测量结果非常吻合，表明组装了核壳、大复合胶束和囊泡形态，粒子形态随混合物的亲水性重量分数（f）而变化。这些纳米结构在存在癌症相关酶 MMP-2 时表现出选择性降解，通过 TEM 和 DLS 都可以探测到形态变化。所有这些结果表明，PVGLIG-b-PTMC 杂化物适合靶向肿瘤微环境。
