Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, PR China.
Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, PR China.
Colloids Surf B Biointerfaces. 2017 Oct 1;158:547-555. doi: 10.1016/j.colsurfb.2017.07.041. Epub 2017 Jul 18.
Hyaluronic acid (HA) is an endogenous polysaccharide that shows intrinsic targetability to CD44+ cancer cells. Here, we developed NIR and UV-responsive degradable nanogels from hyaluronic acid-g-7-N,N-diethylamino-4-hydroxymethylcoumarin (HA-CM) for CD44 targeted and remotely controlled intracellular doxorubicin (DOX) delivery. Nanometer-sized HA-CM nanogels could readily load DOX, and both NIR and UV irradiation could significantly enhance DOX release from the nanogels, resulting from light-triggered cleavage of urethane bonds that connect CM to HA. MTT assays showed that DOX-loaded HA-CM nanogels combined with NIR irradiation induced much higher antitumor activity to MCF-7 cells (CD44+) than to U-87MG cells (CD44-) and free HA pretreated MCF-7 cells. CLSM observations confirmed that DOX-loaded HA-CM nanogels were internalized by CD44+ cells via receptor mediated endocytosis mechanism, and intracellular DOX release was triggered by NIR. These HA-CM nanogels with easy preparation, CD44 targetability and photo-controlled intracellular drug release are interesting for cancer chemotherapy.
透明质酸（HA）是一种内源性多糖，对 CD44+癌细胞具有固有靶向性。在这里，我们开发了一种由透明质酸-g-7-N，N-二乙基氨基-4-羟甲基香豆素（HA-CM）制成的近红外和紫外响应可降解纳米凝胶，用于 CD44 靶向和远程控制细胞内阿霉素（DOX）的递送。纳米尺寸的 HA-CM 纳米凝胶可以很容易地装载 DOX，近红外和紫外光照射均可显著增强纳米凝胶中 DOX 的释放，这是由于连接 CM 和 HA 的氨酯键被光触发断裂所致。MTT 分析表明，载 DOX 的 HA-CM 纳米凝胶与近红外照射联合使用，对 MCF-7 细胞（CD44+）的抗肿瘤活性远高于 U-87MG 细胞（CD44-）和用 HA 预处理的 MCF-7 细胞。CLSM 观察证实，载 DOX 的 HA-CM 纳米凝胶通过受体介导的内吞作用被 CD44+细胞内化，并且近红外光可触发细胞内 DOX 的释放。这些 HA-CM 纳米凝胶具有易于制备、CD44 靶向性和光控细胞内药物释放的特点，对于癌症化疗具有重要意义。
