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金纳米粒子增强的高效双重递药系统用于 HeLa 细胞的抗癌治疗。

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells.

机构信息

Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, 610054, Chengdu, China.

Materials Science Division, Argonne National Laboratory, Argonne, IL, 60439, USA.

出版信息

Sci Rep. 2018 Feb 13;8(1):2907. doi: 10.1038/s41598-018-21331-y.

Abstract

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy of the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.

摘要

胶体金纳米粒子(AuNPs)由于其具有广泛的比表面积和通过表面化学修饰其电荷、亲水性和功能的可能性等先进特性,因此作为药物传递的无毒载体而受到关注。迄今为止,已经使用各种生物相容性聚合物对 AuNPs 进行表面修饰,以提高其稳定性、载药量和细胞摄取率。本研究描述了一种简便的一步法,用于合成稳定的负载两种抗癌治疗药物-博来霉素和阿霉素的 AuNPs。在 HeLa 细胞中证明了 AuNPs 的抗癌活性、细胞毒性、摄取和细胞内定位。我们表明,通过纳米级递药系统对 HeLa 细胞的主动靶向,纳米杂化药物的治疗效果得到了显著增强,通过阻断 HeLa 癌细胞周期,使半最大有效药物浓度显著降低。这些结果为进一步推进使用两种药物的 AuNPs 辅助联合化疗提供了依据,这两种药物通过不同的机制发挥作用,从而降低了癌症耐药性发展的可能性、减少了全身药物毒性,并改善了化疗的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40f7/5811504/e68c660e11ca/41598_2018_21331_Fig1_HTML.jpg

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