Tumor-targeting core-shell structured nanoparticles for drug procedural controlled release and cancer sonodynamic combined therapy
Tumor-targeting core-shell structured nanoparticles for drug procedural controlled release and cancer sonodynamic combined therapy
复制标题
用于药物程序控释和癌症声动力联合治疗的肿瘤靶向核壳结构纳米颗粒
DOI：
10.1016/j.jconrel.2018.07.028
复制
发表时间：
2018-09-28
影响因子：
10.8
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Wang, Lei;Hu, Yujie;Zhang, Yun
多种药物或/和多种辅助治疗的联合治疗已成为肿瘤治疗的热点。本研究以聚乳酸-羟基乙酸共聚物（PLGA，内核）和透明质酸（HA，外壳）为基础，构建了一种新型的核-壳结构的双层给药系统。首先，将HA与PLGA偶联，制备HA-PLGA嵌段共聚物。其次，将5-氨基乙酰丙酸（ALA）通过pH敏感的腙键连接到PLGA上，合成PLGA-HBA-ALA。最后，采用自组装方法构建了以PLGA为核的青蒿素核壳纳米粒（HA-PLGA@ART/ALA NPs）。在该共递送系统中，ALA和ART可以以程序控制释放的方式释放。首先通过pH敏感的腙键裂解从NP释放ALA，以产生用于血红素形成的原卟啉IX（PpIX）。血红素的增加可以有效提高后续释放ART的疗效。此外，该系统还表现出明显的声动力学活性，可用于肿瘤声动力学联合治疗。体内外抗癌实验结果表明，HA-PLGA@ART/ALA给药系统可为肿瘤治疗提供一种有前景的综合治疗策略。
Combination therapy with multiple drugs or/and multiple assistant treatments has become a hot spot in cancer therapy. In this study, a new type of core-shell structured dual-drug delivery system based on poly (lactic-co-glycolic acid) (PLGA, inner cores) and hyaluronic acid (HA, outer shells) was constructed. Firstly, HA was conjugated to PLGA for preparation of HA-PLGA block copolymer. Secondly, 5-amino levulinic acid (ALA) was connected to PLGA through a pH-sensitive hydrazone bond for synthesization of PLGA-HBA-ALA. Finally, the core-shell structured nanoparticles (HA-PLGA@ART/ALA NPs) were constructed by self-assembled method for artemisinin (ART) loading in PLGA cores. In this co-delivery system, ALA and ART can be released in a manner of procedural controlled release. ALA was released from the NPs at first though the pH sensitive hydrazone bond cleavage in order to generate protoporphyrin IX (PpIX) for heme formation. And the increase of heme can effectively improve the curative effect of the subsequent released ART. Furthermore, this system has also shown obvious sonodynaimc activity which can be used for cancer sonodynamic combination therapy. The in vitro and in vivo anticancer results demonstrate that HA-PLGA@ART/ALA delivery system could provide a prospective comprehensive treatment strategy for cancer therapy.