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pH sensitive doxorubicin-loaded nanoparticle based on Radix pseudostellariae protein-polysaccharide conjugate and its improvement on HepG2 cellular uptake of doxorubicin.
Food and Chemical Toxicology ( IF 4.3 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.fct.2019.111099
Xixi Cai 1 , Qian Yang 2 , Qingxia Weng 2 , Shaoyun Wang 2
Affiliation  

Nanoparticles based on Radix pseudostellariae protein-polysaccharide conjugates were self-assembled via pH adjustment and thermal treatment. The fabricated nanoparticles (CP3) were spherical with narrow size distribution of 125.0 nm in diameter. The doxorubicin (DOX) -loaded CP3 nanoparticles exhibited pH-sensitive release behavior and accelerated the release of DOX under the acidic pH simulating tumor microenvironment and endosomal pH. In HepG2 uptake studies, CP3-DOX nanoparticles notably improved the internalization of DOX, which was 1.56-fold compared with free DOX. CP3-DOX nanoparticles could serve as P-glycoprotein efflux pump inhibitor and be internalized into HepG2 cells via clathrin-dependent endocytosis. Moreover, the cytotoxicity effect of DOX on HepG2 cells was elevated after the encapsulation by CP3, with a lower IC50 value of 0.25 μg/mL. The findings suggested that the pH-sensitive CP3-DOX nanoparticles has a great potential in facilitating the efficacy of DOX in cancer cells, and the obtained CP3 could be a good candidate as nanocarrier for the encapsulation and delivery of functional compounds.

中文翻译:

pH敏感的负载阿霉素的纳米颗粒蛋白-多糖缀合物对阿霉素的纳米颗粒及其对HepG2细胞对阿霉素的摄取的改善。

通过酸碱度调节和热处理,可将基于伪星蛋白-多糖共轭物的纳米粒子进行自组装。制成的纳米粒子(CP3)为球形,直径分布狭窄,直径为125.0 nm。载有阿霉素(CP)的阿霉素(CPX)纳米颗粒在模拟肿瘤微环境和内体pH的酸性pH下表现出pH敏感的释放行为,并加速了DOX的释放。在HepG2摄取研究中,CP3-DOX纳米颗粒显着改善了DOX的内在化,与游离DOX相比,后者的1.56倍。CP3-DOX纳米粒子可以充当P-糖蛋白外排泵抑制剂,并通过网格蛋白依赖性内吞作用被内化到HepG2细胞中。此外,CP3封装后,DOX对HepG2细胞的细胞毒性作用增强,其IC50值较低,为0。25微克/毫升 这些发现表明,pH敏感的CP3-DOX纳米粒子在促进DOX在癌细胞中的功效方面具有巨大潜力,并且所获得的CP3可以作为纳米载体用于封装和递送功能化合物的良好候选者。
更新日期:2019-12-27
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