Grenoble Alpes University, CERMAV-CNRS, Grenoble, France.
Nanoscale. 2017 Aug 24;9(33):12150-12162. doi: 10.1039/c7nr03964f.
Multi-stimuli responsive nanogels based on biocompatible hydrophilic polymers have emerged as promising drug delivery systems to improve anticancer therapy with hydrophobic drugs, through increase of circulating-time in the bloodstream, tumor-targeting and reduction of systemic toxicity. This paper reports on the synthesis, characterization and biological perspectives of light- and thermoresponsive hyaluronic acid (HA)-based nanogels containing coumarin as the photocleavable group. Newly synthesized nanogels exhibited interesting features: formation by a temperature-triggered self-assembly process, successful incorporation of poorly water-soluble molecules, light-responsiveness as demonstrated by a significant shift in the critical aggregation temperature after light irradiation, efficient internalization by cancer cells overexpressing the CD44 receptor of HA, ability to circulate for a prolonged period of time in the bloodstream after intravenous injection in mice and considerable detection in tumor tissues. Our findings indicate that coumarin-containing HA-based nanogels may be promising delivery systems for anticancer chemotherapy.
基于生物相容性亲水聚合物的多刺激响应纳米凝胶已成为有前途的药物递送系统，可通过增加血液循环中的循环时间、肿瘤靶向和降低系统毒性来改善疏水性药物的抗癌治疗。本文报道了光和温敏性透明质酸 (HA) 基纳米凝胶的合成、表征和生物学研究，其中包含香豆素作为光裂解基团。新合成的纳米凝胶表现出有趣的特性：通过温度触发的自组装过程形成，成功地掺入了疏水性分子，光响应性表现为光照射后临界聚集温度有明显的变化，通过过表达 HA 的 CD44 受体的癌细胞有效内化，在小鼠静脉注射后能在血液中长时间循环，并在肿瘤组织中得到大量检测。我们的研究结果表明，含香豆素的 HA 基纳米凝胶可能是一种有前途的抗癌化疗药物递送系统。
