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[阿霉素在纳米球中的载体化及肿瘤细胞多药耐药性的逆转]

[Vectorisation of doxorubicin in nanospheres and reversion of pleiotropic resistance of tumor cells].

作者信息

Treupel L, Poupon M F, Couvreur P, Puisieux F

机构信息

U.R.A.-C.N.R.S. no 1218, Faculté de Pharmacie, Châtenay-Malabry.

出版信息

C R Acad Sci III. 1991;313(3):171-4.

PMID:1913255
Abstract

A multidrug resistance human cell line (Dox-R-MCF7), originating from mammary adenocarcinoma was compared to the drug sensitive parent line (MCF7) to determine whether or not the use of doxorubicin-loaded biodegradable nanospheres (NS-Dox) could circumvent drug resistance. The Dox-R-MCF7 line was shown to resist free doxorubicin (Dox) as the 50% lethal dose for them was 150 times higher than for the sensitive cell-line. Isohexylcyanoacrylate nanospheres, porous matrices of biodegradable innocuous polymer, diameter 300 nm, were loaded with doxorubicin. Free Dox, NS-Dox and Dox-free polymer (NS) were added to the culture medium for 6 hrs. In terms of 50% lethal dose, NS-Dox were cytotoxic for the resistant cell line to an identical extent as for the sensitive parent line. Dox-free nanospheres alone or mixed with free-Dox were noncytotoxic for the resistant line. Drug targetting could be of main importance to overcome multidrug resistance.

摘要

将源自乳腺腺癌的多药耐药人细胞系(阿霉素耐药 - MCF7)与药物敏感的亲代细胞系(MCF7)进行比较,以确定使用载有阿霉素的可生物降解纳米球(NS - Dox)是否能够克服耐药性。结果表明,阿霉素耐药 - MCF7细胞系对游离阿霉素(Dox)具有抗性,因为其50%致死剂量比敏感细胞系高150倍。将直径为300 nm的异己基氰基丙烯酸酯纳米球(一种可生物降解的无毒聚合物多孔基质)装载阿霉素。将游离阿霉素、NS - Dox和无阿霉素聚合物(NS)添加到培养基中6小时。就50%致死剂量而言,NS - Dox对耐药细胞系的细胞毒性与对敏感亲代细胞系的细胞毒性程度相同。单独的无阿霉素纳米球或与游离阿霉素混合的纳米球对耐药细胞系无细胞毒性。药物靶向对于克服多药耐药可能至关重要。

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