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载盐酸多柔比星的非离子表面活性剂囊泡用于治疗转移性和非转移性乳腺癌。

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

作者信息

Di Francesco Martina, Celia Christian, Cristiano Maria Chiara, d'Avanzo Nicola, Ruozi Barbara, Mircioiu Constantin, Cosco Donato, Di Marzio Luisa, Fresta Massimo

机构信息

Department of Health Sciences, University of Catanzaro "Magna Graecia", Campus Universitario "S. Venuta" s.n.c., 88100 Catanzaro, Italy.

Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.

出版信息

ACS Omega. 2021 Jan 22;6(4):2973-2989. doi: 10.1021/acsomega.0c05350. eCollection 2021 Feb 2.

Abstract

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.

摘要

盐酸多柔比星(DOX)目前用于治疗原位和转移性乳腺癌。由于其副作用,DOX在癌症患者中的使用有时受到限制;因此,几位科学家尝试设计药物递送系统,以提高药物治疗效果并降低其副作用。在本研究中,我们设计、制备并对非离子表面活性剂囊泡(NSV)进行了物理化学表征,NSV是通过将亲水性(吐温20)和疏水性(司盘20)表面活性剂与胆固醇的不同组合进行自组装而获得的。使用被动和pH梯度远程加载程序将DOX加载到NSV中,这使药物加载量从约1%增加到约45%。对NSV进行了尺寸、形状、尺寸分布、zeta电位、长期稳定性、包封率和释放动力学分析,并选择具有最佳物理化学参数的纳米载体进行进一步测试。含DOX和不含DOX的NSV均稳定,并显示出长达72小时的持续药物释放。对MCF-7和MDA MB 468细胞的研究表明,含有司盘20的NSV比含有吐温20的NSV在MCF-7和MDA MB 468细胞中的内化效果更好。NSV增强了DOX对MCF-7和MDA MB 468细胞的抗癌作用,且这种作用具有时间和剂量依赖性。使用转移性和非转移性乳腺癌细胞的研究还表明,含有司盘20的NSV比含有吐温20的NSV具有更高的细胞毒性。所得数据表明,负载DOX的NSV可能是一种有前途的纳米载体,用于潜在治疗转移性乳腺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f893/7860091/c34b6566a244/ao0c05350_0002.jpg

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