Ciancone Mathieu, Mebrouk Kenny, Bellec Nathalie, Le Goff-Gaillard Catherine, Arlot-Bonnemains Yannick, Benvegnu Thierry, Fourmigué Marc, Camerel Franck, Cammas-Marion Sandrine
Univ Rennes, ENSCR, CNRS, ISCR (Institut des Sciences Chimiques de Rennes), UMR 6226, 35000 Rennes, France.
J Mater Chem B. 2018 Mar 28;6(12):1744-1753. doi: 10.1039/c7tb03289g. Epub 2018 Mar 5.
Biocompatible nanoparticles (NPs) constituted by amphiphilic poly(ethylene glycol)-block-poly(benzyl malate), PEG-b-PMLABe, have been designed for site-specific PhotoThermal Controlled Release (PTCR) of drugs thanks to the presence of a near infra-red (NIR) photothermally active nickel-bis(dithiolene) complex in the inner core of the NPs, together with doxorubicin (Dox). A nanoprecipitation technique was used to prepare well-defined nickel-bis(dithiolene) and nickel-bis(dithiolene)/Dox loaded NPs, which were characterized by dynamic light scattering (DLS), zeta-potential measurements and Transmission Electron Microscopy (TEM). We have shown that the Dox release was effectively controlled by NIR irradiation (long or pulsed NIR laser irradiation). Cytotoxicity experiments on HeLa and MDA-MB-231 cells have shown that the incorporation of more than 10 w% of nickel-bis(dithiolene) complexes does not increase the intrinsic toxicity of the polymer nanoparticles. Finally, the viability of MDA-MB-231 cells was assessed after their incubation, for 24 hours, with empty NPs, Ni4C loaded NPs, Dox loaded NPs or Ni4C/Dox loaded NPs, without or with NIR irradiation. Above all, the results have highlighted that the Ni4C loaded NPs after 5 min NIR laser irradiation can induce strong cell death up to 80% at 50 μg mL. These results demonstrate that these NPs are good candidates for photothermal therapy.
两亲性聚（乙二醇）-嵌段-聚（苄基苹果酸）（PEG-b-PMLABe）构成的生物相容性纳米颗粒（NPs），由于在纳米颗粒内核中存在近红外（NIR）光热活性镍双（二硫纶）配合物以及阿霉素（Dox），已被设计用于药物的位点特异性光热控释（PTCR）。采用纳米沉淀技术制备了明确的负载镍双（二硫纶）和镍双（二硫纶）/阿霉素的纳米颗粒，通过动态光散射（DLS）、ζ电位测量和透射电子显微镜（TEM）对其进行了表征。我们已经表明，阿霉素的释放可通过近红外照射（长波或脉冲近红外激光照射）有效控制。对HeLa和MDA-MB-231细胞进行的细胞毒性实验表明，掺入超过10 w%的镍双（二硫纶）配合物不会增加聚合物纳米颗粒的内在毒性。最后，在MDA-MB-231细胞与空纳米颗粒、负载Ni4C的纳米颗粒、负载阿霉素的纳米颗粒或负载Ni4C/阿霉素的纳米颗粒孵育24小时后，在有无近红外照射的情况下评估其活力。最重要的是，结果突出表明，50 μg/mL的负载Ni4C的纳米颗粒在5分钟近红外激光照射后可诱导高达80%的强烈细胞死亡。这些结果表明，这些纳米颗粒是光热疗法的良好候选者。
