Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
Department of Oncology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou 646000, China.
Int J Pharm. 2020 Nov 15;589:119875. doi: 10.1016/j.ijpharm.2020.119875. Epub 2020 Sep 9.
Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.
多药化疗一直是治疗恶性肿瘤的最流行策略之一,并取得了理想的治疗效果。本研究旨在开发可生物降解的 PCEC 纳米粒子(NPs)用于紫杉醇(PTX)和姜黄素(CUR)的共递送,并研究该药物递送系统(DDS:PTX-CUR-NPs)在体外和体内对乳腺癌的抗肿瘤作用。所制备的 PTX-CUR-NPs 具有小尺寸为 27.97 ± 1.87nm,低多分散指数(PDI,0.197 ± 0.040)。结果表明,PTX 和 CUR 从 DDS 中缓慢释放,没有任何突释效应。此外,PTX-CUR-NPs 在 MCF-7 细胞中表现出剂量依赖性细胞毒性,其凋亡率(64.29% ± 1.97%)高于游离药物(PTX + CUR,34.21% ± 0.81%)。细胞摄取研究表明,载药 PCEC 聚合物纳米粒子更容易被肿瘤细胞摄取。为了评估体内抗肿瘤作用,将 PTX-CUR-NPs 静脉注射到荷 MCF-7 细胞的 BALB/c 裸鼠中,结果表明与游离药物(PTX + CUR)相比,肿瘤生长受到显著抑制,生存时间延长,副作用减少。此外,与其他治疗组相比,PTX-CUR-NPs 治疗组肿瘤细胞中的 Ki67 表达降低(p < 0.05),TUNEL 阳性率升高(凋亡增加,p < 0.01),提示该 DDS 的治疗效果。总之,本研究表明,PTX-CUR-NPs DDS 可用于未来有效治疗乳腺癌。