Synergistic effect of DR5-targeted capsules loaded with doxorubicin in drug-resistant 3D tumour spheroids.

IF 3.2 4区医学 Q2 CHEMISTRY, APPLIED

Journal of microencapsulation Pub Date : 2025-10-14 DOI:10.1080/02652048.2025.2570651

Daria Trushina, Anastasia Gileva, Anne Yagolovich, Marine Gasparian, Leyli Kurbanova, Sergey Burov, Tatiana Bukreeva, Tatiana Pallaeva, Vladimir Artemov, Vladimir Oleinikov, Elena Markvicheva

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引用次数: 0

Abstract

Aim: To develop polyelectrolyte multilayer capsules (PMC) loaded with doxorubicin (DOX) and modified with the DR5-B protein to overcome drug resistance in MCF-7 breast cancer cells.

Methods: The capsules were prepared by layer-by-layer (LbL) assembly followed by thermal shrinking, DOX encapsulation and DR5-B surface modification. The capsules were characterised using scanning electron microscopy (SEM), dynamic light scattering (DLS), and UV-Vis spectrophotometry. Cellular uptake was assessed by confocal microscopy, flow cytometry, and fluorimetry. Cytotoxicity was evaluated by MTT-test in 2D and 3D in vitro models.

Results: Mean capsule size was 320 ± 90 nm (PDI 0.39), mean ζ-potential was +29 ± 5 mV. The encapsulation efficiencies (ЕЕ) of DOX and DR5-B were 85 ± 7% and 80 ± 4%, with loading capacities (LC) of 9 ± 2 w/w% and 145 ± 40 w/w%, respectively. Shrunken capsules exhibited 3.5-fold higher internalisation than non-shrunken ones. DR5-B increased capsule accumulation by 1.8-fold. The capsules showed synergistic cytotoxicity in DR5-B-resistant MCF-7 spheroids (IC50 227 ± 13 ng/mL), being non-toxic to fibroblasts.

查看原文本刊更多论文

载多柔比星dr5靶向胶囊在耐药三维肿瘤球体中的协同作用。

目的：制备负载多柔比星（DOX）并经DR5-B蛋白修饰的聚电解质多层胶囊（PMC），以克服MCF-7乳腺癌细胞的耐药。方法：采用逐层组装法制备微胶囊，热收缩、DOX包封、DR5-B表面改性。采用扫描电子显微镜（SEM）、动态光散射（DLS）和紫外可见分光光度法对胶囊进行表征。通过共聚焦显微镜、流式细胞术和荧光法评估细胞摄取。采用mtt试验对体外模型进行二维和三维细胞毒性评价。结果：平均胶囊大小为320±90 nm (PDI 0.39)，平均ζ电位为+29±5 mV。DOX和DR5-B的包封效率（ЕЕ）分别为85±7%和80±4%，载药量（LC）分别为9±2 w/w%和145±40 w/w%。收缩胶囊的内化程度比未收缩胶囊高3.5倍。DR5-B使胶囊积累增加1.8倍。该胶囊对耐dr5 - b的MCF-7球体具有协同细胞毒性（IC50为227±13 ng/mL），对成纤维细胞无毒。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of microencapsulation 工程技术-工程：化工

CiteScore

6.30

自引率

2.60%

发文量

审稿时长

3 months

期刊介绍： The Journal of Microencapsulation is a well-established, peer-reviewed journal dedicated to the publication of original research findings related to the preparation, properties and uses of individually encapsulated novel small particles, as well as significant improvements to tried-and-tested techniques relevant to micro and nano particles and their use in a wide variety of industrial, engineering, pharmaceutical, biotechnology and research applications. Its scope extends beyond conventional microcapsules to all other small particulate systems such as self assembling structures that involve preparative manipulation. The journal covers: Chemistry of encapsulation materials Physics of release through the capsule wall and/or desorption from carrier Techniques of preparation, content and storage Many uses to which microcapsules are put.