Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.
Cancer cell targeting, controlled drug release and intracellular fate of biomimetic membrane-encapsulated drug-loaded nano-graphene oxide nanohybrids.
复制标题
仿生膜封装载药纳米氧化石墨烯纳米杂化物的癌细胞靶向、受控药物释放和细胞内命运
DOI：
10.1039/c8tb00804c
复制
发表时间：
2018-08-21
期刊：
影响因子：
--
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Ma K;Fu D;Liu Y;Rui Dai;Yu D;Guo Z;Cui C;Wang L;Xu J;Mao C
纳米氧化石墨烯（NGO）已被提议作为一种新型药物载体。然而，生物相容性和生理稳定性差以及缺乏癌症靶向能力限制了其在癌症治疗中的进一步应用。为了解决这个问题，我们开发了一种新型的NGO/DOX@SPC-FA纳米杂化物，首先让大豆磷脂酰胆碱膜（SPC）封装负载DOX的NGO（NGO/DOX），然后用聚乙二醇化脂质-FA缀合物修饰SPC膜，以实现在纳米杂化物表面展示癌症靶向FA。 SPC膜（模拟细胞膜）使所得纳米杂化物（NGO/DOX@SPC-FA）表现出良好的稳定性和生物相容性、高载药能力、高效的细胞摄取和受控的药物释放。此外，与NGO/DOX和SPC修饰的NGO/DOX（NGO/DOX@SPC）相比，FA修饰的NGO/DOX@SPC纳米杂化物（NGO/DOX@SPC-FA）由于表面存在FA靶向基序，可以将NGO/DOX递送至癌细胞，并提高递送和杀伤功效。 NGO/DOX@SPC-FA 纳米杂化物被发现通过巨胞饮作用定向的吞噬作用和网格蛋白依赖性内吞作用被 FA 阳性癌细胞（Hela 细胞）特异性内化，然后定位到溶酶体中。体内生物分布研究表明，由于叶酸修饰的主动靶向机制，NGO/DOX@SPC-FA具有较高的肿瘤靶向能力。体内抗肿瘤治疗研究表明NGO/DOX@SPC-FA能够显着抑制肿瘤生长并延长小鼠的生存时间。我们的结果表明，NGO/DOX@SPC-FA 作为一种具有高载药量和靶向递送效率的新型药物递送系统，为未来的癌症治疗带来了希望。 FA 修饰的 NGO/DOX@SPC-FA 纳米杂化物可以将 DOX 递送至癌细胞和肿瘤组织，并提高递送和抑制功效。
Nano-graphene oxide (NGO) has been proposed as a novel drug carrier. However, the poor biocompatibility and physiological stability as well as lack of cancer targeting capability have limited its further applications in cancer therapy. To solve this problem, we developed a novel nanohybrid of NGO/DOX@SPC-FA by first allowing soy phosphatidylcholine membrane (SPC) to encapsulate DOX-loaded NGO (NGO/DOX) and then modifying the SPC membrane with PEGylated lipid-FA conjugate to achieve the display of cancer targeting FA on the nanohybrid surface. The SPC membrane (mimicking cell membrane) enabled the resultant nanohybrids (NGO/DOX@SPC-FA) to exhibit good stability and biocompatibility, high drug loading capability, efficient cellular uptake, and controlled drug release. Moreover, compared with NGO/DOX and SPC-modified NGO/DOX (NGO/DOX@SPC), the FA-modified NGO/DOX@SPC nanohybrids (NGO/DOX@SPC-FA) could deliver NGO/DOX to cancer cells with improved delivery and killing efficacy due to the presence of FA targeting motifs on the surface. The NGO/DOX@SPC-FA nanohybrids were found to be internalized specifically by FA-positive cancer cells (Hela cells) through both macropinocytosis-directed engulfment and clathrin-dependent endocytosis, and then become localized into the lysosomes. In vivo biodistribution study showed that NGO/DOX@SPC-FA had a high tumor targeting ability because of the active targeting mechanism with folate modification. In vivo antitumor therapy study demonstrated NGO/DOX@SPC-FA could significantly inhibit tumour growth and prolong the survival time of mice. Our results suggest that NGO/DOX@SPC-FA, as a novel drug delivery system with high drug loading and targeted delivery efficiency, holds promise for future cancer therapy. The FA-modified nanohybrids of NGO/DOX@SPC-FA could deliver DOX to cancer cells and tumor tissues with improved delivery and inhibition efficacy.