卡莫司汀和卡巴他赛联合给药脂质体制剂的制备提高了细胞毒性潜力,并诱导卵巢癌细胞凋亡。

IF 3.6 4区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of Biomaterials Science, Polymer Edition Pub Date : 2024-08-29 DOI:10.1080/09205063.2024.2387949
Jianming Gong, Renqian Feng, Xiaoqing Fu, Qi Lin, Bicheng Wu
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引用次数: 0

摘要

卵巢癌是女性患者死于癌症的主要原因。现有的卵巢癌治疗方法受到限制,无法有效治愈该疾病。为解决这一问题,我们提供了一种治疗卵巢癌的新方法,即利用脂质体载体有效递送化疗药物卡莫司汀(BCNU)和卡巴齐他赛(CTX)。最初,BCNU 和 CTX 的联合作用得到了证实,发现这种作用在 1:2 mol/mol(BCNU/CTX)的比例时达到最大。随后,开发出了 BC-Lipo 联合给药系统,该系统具有很高的载药能力(BCNU 为 97.48% ± 1.14,CTX 为 86.29% ± 3.03)。该系统还具有持续释放特性和有益的长循环特性。与游离药物相比,BC-Lipo 在肿瘤中的蓄积显著增加。此外,在体外模型中对 HeLa 细胞进行测试时,BC-Lipo 表现出与游离 BCNU 和 CTX(BCNU/CTX)相似的细胞毒性水平。生化染色法研究了癌细胞的形态学检查。流式细胞仪分析法通过 FITC-Annexin-V/PI 染色证实了细胞凋亡。此外,荧光和蛋白质标记物的研究还考察了细胞凋亡的机理途径,结果表明 BC-Lipo 诱导细胞凋亡是由于线粒体膜电位的变化。这项概念验证研究确定了这些 BCNU-CTX 联合疗法作为活性给药纳米载体用于溶解性较差的 BCNU 和 CTX 的可能性。
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Fabrication of co-delivery liposomal formulation incorporating carmustine and cabazitaxel displays improved cytotoxic potential and induced apoptosis in ovarian cancer cells.

Ovarian cancer is the primary cause of death from cancer in female patients. The existing treatments for ovarian cancer are restricted and ineffective in achieving a cure for the disease. To address this issue, we provide a novel approach to treating ovarian cancer by utilizing a liposomal carrier that effectively delivers the chemotherapeutic drugs carmustine (BCNU) and cabazitaxel (CTX). Initially, the combined impact of BCNU and CTX was confirmed, revealing that this impact reaches its maximum at a ratio of 1:2 mol/mol (BCNU/CTX). After that, the BC-Lipo co-delivery system was developed, which has a high capability for loading drugs (97.48% ± 1.14 for BCNU, 86.29% ± 3.03 for CTX). This system also has a sustained release profile and a beneficial long-circulating feature. The accumulation of BC-Lipo in tumors was dramatically enhanced compared to the accumulation of the free drug. Furthermore, BC-Lipo demonstrated similar levels of cytotoxicity to free BCNU and CTX (BCNU/CTX) when tested on HeLa cells in an in vitro model. Biochemical staining methods investigated the cancer cell's morphological examination. The apoptosis was confirmed by FITC-Annexin-V/PI staining by flow cytometry analysis. In addition, the investigation of fluorescence and protein markers examined the apoptosis mechanistic pathway, and the results indicated that BC-Lipo induced apoptosis due to mitochondrial membrane potential variation. This proof-of-concept study has established the probability of these BCNU-CTX combined treatments as active drug delivery nanocarriers for poorly soluble BCNU and CTX.

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来源期刊
Journal of Biomaterials Science, Polymer Edition
Journal of Biomaterials Science, Polymer Edition 工程技术-材料科学:生物材料
CiteScore
7.10
自引率
5.60%
发文量
117
审稿时长
1.5 months
期刊介绍: The Journal of Biomaterials Science, Polymer Edition publishes fundamental research on the properties of polymeric biomaterials and the mechanisms of interaction between such biomaterials and living organisms, with special emphasis on the molecular and cellular levels. The scope of the journal includes polymers for drug delivery, tissue engineering, large molecules in living organisms like DNA, proteins and more. As such, the Journal of Biomaterials Science, Polymer Edition combines biomaterials applications in biomedical, pharmaceutical and biological fields.
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