Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid.
Nanoparticle delivery and combination therapy of gambogic acid and all-trans retinoic acid.
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藤黄酸和全反式视黄酸的纳米颗粒递送和联合治疗
DOI：
10.2147/ijn.s62793
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发表时间：
2014
影响因子：
8
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Yao J;Li Y;Sun X;Dahmani FZ;Liu H;Zhou J
为了提高藤黄酸（GA）和全反式维甲酸（ATRA）的体内共递送效率，我们将GA包埋在基于两亲性透明质酸（HA）-全反式维甲酸（HRA）偶联物的自组装纳米粒中。以这种方式，GA和ATRA同时装载在纳米载体中，并通过HA受体介导的内吞作用共同递送到肿瘤细胞中。采用透析法制备了GA-HRA纳米粒，并对其理化性质进行了研究。GA-HRA具有较高的载药量（31.1%），粒径在100-150 nm之间，生物相容性良好。HRA纳米颗粒被MCF-7细胞有效地内化，并以时间依赖性的方式易位到细胞核中。体内成像分析表明，与游离DiR溶液相比，静脉给药后，DiR负载的纳米颗粒在肿瘤中的荧光信号显著增加，表明其具有优异的肿瘤靶向性。更重要的是，GA-HRA表现出优异的体内功效，毒性显著降低。因此，在HRA纳米颗粒的辅助下，GA和ATRA可以成功地实现有效的联合化疗以及肿瘤靶向递送。
In order to enhance the in vivo codelivery efficiency of gambogic acid (GA) and all-trans retinoic acid (ATRA), our strategy was to entrap GA in the self-assembled nanoparticles based on amphiphilic hyaluronic acid (HA)-ATRA (HRA) conjugate. In this way, GA and ATRA were loaded simultaneously in a nanocarrier and codelivered into the tumor cell through HA receptor-mediated endocytosis. GA-loaded HRA nanoparticles (GA-HRA) were prepared by a dialysis method, and their physicochemical characteristics were investigated as well. GA-HRA exhibited a high drug loading capacity (31.1%), had a particle size in the range of 100–150 nm, and good biocompatibility. HRA nanoparticles were effectively internalized by MCF-7 cells and translocated into the nucleus in a time-dependent manner. The in vivo imaging analysis demonstrated that the fluorescent signals in the tumor were markedly increased with DiR-loaded nanoparticles after intravenous administration compared to free DiR solution, suggesting it has excellent tumor targeting properties. More importantly, GA-HRA exhibited excellent in vivo efficacy with dramatically reduced toxicity. In conclusion, with the assistance of HRA nanoparticles, GA and ATRA can successfully realize an effective combination chemotherapy as well as tumor-targeted delivery.