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化疗药物预处理以增强纳米颗粒在肿瘤中的积累:G2期周期阻滞效应的潜在作用

Pretreatment with chemotherapeutics for enhanced nanoparticles accumulation in tumor: the potential role of G2 cycle retention effect.

作者信息

Gao Huile, Hu Guanlian, Zhang Qianyu, Zhang Shuang, Jiang Xinguo, He Qin

机构信息

Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University; No.17 Block 3, Southern Renmin Road, Chengdu, 610041, China.

Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education; School of Pharmacy, Fudan University; 826 Zhangheng Road, Shanghai, 201203, China.

出版信息

Sci Rep. 2014 Mar 27;4:4492. doi: 10.1038/srep04492.

Abstract

Ligands were anchored onto nanoparticles (NPs) to improve the cell internalization and tumor localization of chemotherapeutics. However, the clinical application was shadowed by the complex preparation procedure and the immunogenicity and poor selectivity and stability of ligands. In this study, a novel strategy was developed to elevate the tumor cellular uptake and tumor localization of NPs utilizing the G2/M phase retention effect of docetaxel, one of the most common chemotherapeutics. Results showed pretreatment with docetaxel could effectively arrest cells in G2/M phase, leading to an enhanced cell uptake of NPs, which may be caused by the facilitated endocytosis of NPs. In vivo imaging and slice distribution also demonstrated the pretreatment with docetaxel improved the localization of NPs in tumor. This strategy can be easily transferred to clinical for cancer management. Combination chemotherapeutics injections with commercial nano-drugs may result in better antitumor effect than the administration of a single drug.

摘要

将配体锚定在纳米颗粒(NPs)上,以改善化疗药物的细胞内化和肿瘤定位。然而,复杂的制备过程以及配体的免疫原性、低选择性和稳定性使得其临床应用受到影响。在本研究中,利用多西他赛(最常用的化疗药物之一)的G2/M期滞留效应,开发了一种新策略来提高纳米颗粒的肿瘤细胞摄取和肿瘤定位。结果表明,多西他赛预处理可有效使细胞停滞于G2/M期,导致纳米颗粒的细胞摄取增加,这可能是由于纳米颗粒的内吞作用增强所致。体内成像和切片分布也表明,多西他赛预处理改善了纳米颗粒在肿瘤中的定位。该策略可轻松转化至临床用于癌症治疗。联合化疗药物注射与商用纳米药物可能比单一药物给药产生更好的抗肿瘤效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba71/3967147/f4c4b9337ad9/srep04492-f1.jpg

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