Double-layered hyaluronic acid/stearic acid-modified polyethyleneimine nanoparticles encapsulating (-)-gossypol: a nanocarrier for chiral anticancer drugs.
Double-layered hyaluronic acid/stearic acid-modified polyethyleneimine nanoparticles encapsulating (-)-gossypol: a nanocarrier for chiral anticancer drugs.
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包裹(-)-棉酚的双层透明质酸/硬脂酸改性聚乙烯亚胺纳米粒子：手性抗癌药物的纳米载体
DOI：
10.1039/c4tb00539b
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发表时间：
2014-08-28
期刊：
影响因子：
--
通讯作者：
Wu D
中科院分区：
文献类型：
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作者：
Liu H;Li K;Lan L;Ma J;Zeng Y;Xu L;Wu D
本研究旨在提高（-）-棉酚的水溶性和抗肿瘤效果。采用硬脂酸共轭聚乙烯亚胺（PgS）对棉酚进行负载，并通过氢键保护棉酚。采用两步法制备了透明质酸（HA）修饰的（-）-棉酚[（-）-G-PgSHAs]双层PgS纳米粒。通过透射电子显微镜和动态光散射分析确定纳米颗粒具有均匀的球形形状，其动态尺寸为110.9 ± 2.4nm。包封率为72.6% ± 3.1%，载药量为9.1% ± 0.42%。样品的红外光谱证实了氢键对包封棉酚光学活性的保护作用。由于HAase在肿瘤区域的高表达，（-）-G-PgSHAs表现出受控的和肿瘤特异性的释放。通过体外细胞摄取和体内近红外荧光成像证实了由于HA受体介导的PgSHAs的肿瘤靶向特征。体外细胞毒性试验表明，（-）-G-PgSHAs与游离（-）-棉酚具有相似的细胞毒性，但小于包封的（±）-棉酚[（±）-G-PgSHAs]。体内抑瘤实验表明，（-）-G-PgSHAs的抑瘤作用明显优于游离（-）-棉酚和（±）-G-PgSHAs（P < 0.05），且全身毒性明显降低。因此，PgSHA是一种有用的（-）-棉酚纳米载体，具有良好的生物相容性，可调的药物释放，和肿瘤靶向特性的癌症治疗。此外，这种双层纳米载体为其他手性药物的包封提供了新的策略。
This study aimed to enhance the water solubility and antitumor efficacy of (-)-gossypol. Polyethyleneimine conjugated with stearic acid (PgS) was used for loading and protecting (-)-gossypol through hydrogen bonding. Double-layered hyaluronic acid (HA)-modified PgS nanoparticles encapsulating (-)-gossypol [(-)-G-PgSHAs] were prepared through a two-step fabrication process. The nanoparticles possessed a uniform spherical shape with a dynamic size of 110.9 ± 2.4 nm, which was determined through transmission electron microscopy and dynamic light scattering analysis. The encapsulation efficiency and drug-loading capacity of (-)-G-PgSHAs were 72.6% ± 3.1% and 9.1% ± 0.42%, respectively. The IR spectra of the samples confirmed the protection effect of hydrogen bonding on the optical activity of the encapsulated (-)-gossypol. (-)-G-PgSHAs exhibited a controlled and tumor-specific release because of the high expression of HAase in the tumor region. The tumor-targeting feature of PgSHAs due to HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near infrared fluorescence imaging. The in vitro test showed that the (-)-G-PgSHAs had similar cytotoxicity to free (-)-gossypol and was smaller than that of the encapsulated (±)-gossypol [(±)-G-PgSHAs]. The in vivo study of the anti-cancer effect of (-)-G-PgSHAs revealed that (-)-G-PgSHAs had a more enhanced tumor-suppression effect and reduced systemic toxicity compared with free (-)-gossypol and (±)-G-PgSHAs (P < 0.05). Therefore, PgSHA was a useful (-)-gossypol nanocarrier that exhibits high biocompatibility, tunable release of drug, and tumor-targeting characteristics for cancer treatment. In addition, this double-layered nanocarrier provided novel strategies for the encapsulation of other chiral drugs.