Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance.
Sericin nanomicelles with enhanced cellular uptake and pH-triggered release of doxorubicin reverse cancer drug resistance.
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丝胶纳米胶束具有增强的细胞摄取和 pH 触发的阿霉素释放，可逆转癌症耐药性
DOI：
10.1080/10717544.2018.1469686
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Guo W;Deng L;Yu J;Chen Z;Woo Y;Liu H;Li T;Lin T;Chen H;Zhao M;Zhang L;Li G;Hu Y
耐药性是癌症化疗面临的主要挑战，基于丝胶等天然材料的纳米缓释系统是克服耐药性的一种有前途的手段。然而，将合成的聚(γ-苄基-L-谷氨酸酯)引入丝胶多肽来制备简单的生物相容和可生物降解的胶束还没有尝试过。在这里，我们通过开环聚合(ROP)策略制备了一种含有亲水性丝胶多肽骨架和PBLG侧链的多肽基两亲性聚合物。PBLG侧链的引入显著提高了丝胶胶束在水中的稳定性。同时，该胶束对抗癌药物阿霉素(DOX)丝胶蛋白-PBLG-DOX具有较高的载药量和pH响应释放能力。由于丝胶-PBLG具有良好的细胞膜穿透性，提高了DOX在胶束中的细胞摄取率。随后，丝胶-PBLG-DOX被转移到核周溶酶体内，从而加快了DOX的释放速度。与相同剂量的DOX相比，丝胶-PBLG-DOX在体外和体内都能诱导出更有效的抗肿瘤作用，这些胶束具有良好的生物安全性、增强的细胞摄取、pH触发的药物释放、有效的抗肿瘤作用和最小的全身毒性，有望在临床上克服肿瘤耐药性。
Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy. The introduction of PBLG side chains remarkably enhances the stability of sericin micelles in water. Meanwhile, the micelles exhibited a high loading capacity and pH-responsive release ability for antitumor drug doxorubicin (DOX), called sericin-PBLG-DOX. Owing to the excellent cell membrane penetration of sericin-PBLG, the cellular uptake of DOX when loaded into micelles was improved. Subsequently, sericin-PBLG-DOX was transferred into perinuclear lysosomes, where the release rate of DOX was accelerated. Compared to the same dose of DOX, sericin-PBLG-DOX could induce a more efficient anti-tumor effect both in vitro and in vivo, and these micelles have promise for future clinical applications in overcoming cancer drug resistance with good biosafety, enhanced cellular uptake, pH-triggered drug release, efficient anti-tumor effects, and minimized systemic toxicity.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
MSN抗癌纳米药物：增强化疗、克服耐药性、抑制转移
影响因子：
29.4
作者：
He, Qianjun;Shi, Jianlin
通讯作者：
Shi, Jianlin
影响因子：
5.8
作者：
Andre, E. M.;Pensado, A.;Montero-Menei, C. N.
通讯作者：
Montero-Menei, C. N.
DOI：
10.3390/molecules21091265
发表时间：
2016-09-21
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Hekmat A;Attar H;Seyf Kordi AA;Iman M;Jaafari MR
通讯作者：
Jaafari MR
设计和制造多功能丝胶纳米粒子，用于癌症化疗药物的肿瘤靶向和 pH 响应亚细胞递送
影响因子：
9.5
作者：
Huang, Lei;Tao, Kaixiong;Wang, Lin
通讯作者：
Wang, Lin