Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, Bangkok 10330, Thailand.
Carbohydr Polym. 2018 Oct 15;198:495-508. doi: 10.1016/j.carbpol.2018.06.119. Epub 2018 Jun 30.
In this work, we report for the first time AuNPs reduced/stabilized/capped with modified para-aminobenzoic acid-quat188-pullulan (PABA-QP) as excellent nanocarriers for delivery of doxorubicin to enhance the activity and safety of these systems. Spherical AuNPs@PABA-QP obtained by facile and green synthesis under optimum conditions were characterized by UV-VIS, TEM, EDS, SAED, XRD, ATR-FTIR and zeta-potential analyses and showed a narrow size distribution of 13.7 ± 1.9 nm. DOX was successfully loaded onto AuNPs@PABA-QP via intermolecular interactions with high drug loading. DOX-AuNPs@PABA-QP (IC = 0.39μM) showed a 2.1-fold higher cytotoxicity against Chago cells than DOX alone (IC = 0.82μM), while exhibiting less cytotoxicity against normal cells (Wi-38). Moreover, DOX-AuNPs@PABA-QP also demonstrated high intracellular uptake by endocytosis, arrested in S and G2-M phases of the cell cycle (total S/G2-M increased to approximately 18.0%), induced excellent cytotoxicity, and increased the fraction of late-apoptotic cells (18.6%). Consequently, it is suggested that the novel combination of DOX-AuNPs@PABA-QP has the potential to be developed for human cancer treatment.
在这项工作中,我们首次报道了 AuNPs 被修饰的对氨基苯甲酸-季铵 188-普鲁兰(PABA-QP)还原/稳定/封端,作为递送阿霉素的优秀纳米载体,以提高这些系统的活性和安全性。在最佳条件下通过简便、绿色的合成方法得到的球形 AuNPs@PABA-QP 采用 UV-VIS、TEM、EDS、SAED、XRD、ATR-FTIR 和 zeta-电位分析进行了表征,显示出 13.7±1.9nm 的窄粒径分布。通过分子间相互作用,成功地将 DOX 负载到 AuNPs@PABA-QP 上,载药率高。与单独使用 DOX(IC=0.82μM)相比,DOX-AuNPs@PABA-QP(IC=0.39μM)对 Chago 细胞的细胞毒性提高了 2.1 倍,而对正常细胞(Wi-38)的细胞毒性则较低。此外,DOX-AuNPs@PABA-QP 还通过内吞作用表现出高的细胞内摄取,细胞周期停滞在 S 和 G2-M 期(总 S/G2-M 增加到约 18.0%),诱导优异的细胞毒性,并增加晚期凋亡细胞的比例(18.6%)。因此,建议将 DOX-AuNPs@PABA-QP 的新组合开发用于人类癌症治疗。