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通过延长内溶酶体囊泡来消除肿瘤外排:低剂量抗癌碳纳米管药物的开发。

Nullifying tumor efflux by prolonged endolysosome vesicles: development of low dose anticancer-carbon nanotube drug.

机构信息

School of Nano & Advanced Materials Science, Bio-Nano-Information Tech. R/D Center and RIGET, Gyeongsang National University , Jinju 660-701, South Korea.

出版信息

ACS Nano. 2013 Oct 22;7(10):8484-97. doi: 10.1021/nn4041206. Epub 2013 Sep 18.

Abstract

As the majority of side effects of current chemotherapies stems from toxicity due to excessive dosing of anticancer drugs, minimizing the amount of drug while maximizing drug efficacy is essential to increase the life-quality of chemotherapy patients. This study demonstrated that the intracellular delivery of amide linked doxorubicin on carbon nanotube can nullify the efflux of cancer cells by achieving prolonged endolysosome delivery and can induce burst release of doxorubicin in an acidic hydrolase environment and, ultimately, can reduce the amount of anticancer drug by 10-fold compared to conventional effective drug dose. The clearance of accumulated carbon nanotubes in the liver was observed after 4 weeks, and analysis of liver toxicity markers showed no significant changes in GOT and GPT levels and release of pro-inflammatory cytokines across both short- and long-term periods.

摘要

由于目前大多数化疗的副作用源于抗癌药物过量使用所导致的毒性,因此减少药物剂量同时最大化药物疗效对于提高化疗患者的生活质量至关重要。本研究表明,通过在碳纳米管上进行酰胺键连接的阿霉素的细胞内传递,可以通过实现延长内溶酶体传递来消除癌细胞的外排作用,并可以在酸性水解酶环境中诱导阿霉素的爆发释放,最终与传统有效药物剂量相比,减少 10 倍的抗癌药物用量。在 4 周后观察到肝脏中积累的碳纳米管的清除,并且对肝毒性标志物的分析显示,在短期和长期内,GOT 和 GPT 水平以及促炎细胞因子的释放均无显著变化。

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