Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis
Co-delivery of doxorubicin and oleanolic acid by triple-sensitive nanocomposite based on chitosan for effective promoting tumor apoptosis
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DOI：
10.1016/j.carbpol.2020.116672
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发表时间：
2020-11-01
影响因子：
11.2
通讯作者：
Zhu, Li-Min
中科院分区：
文献类型：
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作者：
Chen, Xia;Niu, Shiwei;Zhu, Li-Min
纳米复合材料作为“搬运工”的多药联合输送具有很大的希望，在解决传统的癌症化疗的缺点。在这项工作中，我们的策略提出了一种新的途径，逐步释放两个共同交付的代理到肿瘤细胞。该杂化纳米复合材料由pH响应性壳聚糖（CS）、温敏性聚（N-乙烯基己内酰胺）（PNVCL）和功能化细胞穿透肽（H6 R6）组成。将多柔比星（DOX）和油酸（OA）负载到纳米复合材料（H6 R6-CS-g-PNVCL）中。该系统显示出合适的尺寸（类似于190 nm）、高DOX负载（13.2%）和OA负载效率（7.3%）。肿瘤微环境触发纳米复合材料选择性地保留在肿瘤细胞中，然后释放药物。体外和体内研究均显示，与单递送相比，共递送系统的抗肿瘤活性显著增强。这种依赖于氧化还原，pH和温度效应的方法，利用共递送纳米系统可能有利于未来在癌症化疗中的应用。
Nanocomposites as "stevedores" for co-delivery of multidrugs hold great promise in addressing the drawbacks of traditional cancer chemotherapy. In this work, our strategy presents a new avenue for the stepwise release of two co-delivered agents into the tumor cells. The hybrid nanocomposite consists of a pH-responsive chitosan (CS), a thermosensitive poly(N-vinylcaprolactam) (PNVCL) and a functionalized cell-penetrating peptide (H6R6). Doxorubicin (DOX) and oleanolic acid (OA) are loaded into the nanocomposite (H6R6-CS-g-PNVCL). The system displayed a suitable size (similar to 190 nm), a high DOX loading (13.2 %) and OA loading efficiency (7.3 %). The tumor microenvironment triggered the nanocomposite to be selectively retained in tumor cells, then releasing the drugs. Both in vitro and in vivo studies showed a significant enhancement in antitumor activity of the co-delivered system in comparison to mono-delivery. This approach which relies on redox, pH and temperature effects utilizing co-delivery nanosystems may be beneficial for future applications in cancer chemotherapy.