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使用脂质纳米制剂共同递送达卡巴嗪和全反式维甲酸(ATRA)以协同对抗恶性黑色素瘤的抗肿瘤功效

Co-delivery of Dacarbazine and All-Trans Retinoic Acid (ATRA) Using Lipid Nanoformulations for Synergistic Antitumor Efficacy Against Malignant Melanoma.

作者信息

Li Chenyang, Han Xiuping

机构信息

Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China.

出版信息

Nanoscale Res Lett. 2020 May 19;15(1):113. doi: 10.1186/s11671-020-3293-3.

Abstract

Malignant melanoma is a highly aggressive skin cancer responsible for 80% of mortality, and the overall median survival in patients with metastatic melanoma is only 6-9 months. Combination treatment through the simultaneous administration of dual drugs in a single nanocarrier has been demonstrated to be elegant and effective in combatting cancer. Herein, we employ a combination therapy based on dacarbazine (DBZ), FDA approved drug for melanoma and all-trans retinoic acid (ATRA), promising anticancer agents loaded on lipid nanoformulations (RD-LNF) as a new treatment strategy for malignant melanoma. We have successfully encapsulated both the drugs in lipid nanoformulations and showed a controlled release of payload over time. We demonstrated that the simultaneous delivery of DBZ and ATRA could effectively reduce cell proliferation in a concentration-dependent manner. The combinational nanoparticles significantly reduced the colony formation ability of B16F10 melanoma cells. Flow cytometer analysis showed that RD-LNF induced a greater proportion of apoptosis cells with significant inhibition of cell cycle progression and cell migration. These results suggest the promising potential of RD-LNF in the treatment of malignant melanoma with high efficacy.

摘要

恶性黑色素瘤是一种极具侵袭性的皮肤癌,占皮肤癌死亡率的80%,转移性黑色素瘤患者的总体中位生存期仅为6至9个月。在单一纳米载体中同时施用两种药物的联合治疗已被证明在对抗癌症方面既巧妙又有效。在此,我们采用基于达卡巴嗪(DBZ,一种经美国食品药品监督管理局批准用于治疗黑色素瘤的药物)和全反式维甲酸(ATRA,一种有前景的抗癌药物)负载于脂质纳米制剂(RD-LNF)的联合疗法,作为恶性黑色素瘤的一种新治疗策略。我们已成功将这两种药物封装在脂质纳米制剂中,并显示出随着时间推移有效载荷的可控释放。我们证明,同时递送DBZ和ATRA能够以浓度依赖的方式有效降低细胞增殖。组合纳米颗粒显著降低了B16F10黑色素瘤细胞的集落形成能力。流式细胞仪分析表明,RD-LNF诱导了更大比例的凋亡细胞,对细胞周期进程和细胞迁移有显著抑制作用。这些结果表明RD-LNF在高效治疗恶性黑色素瘤方面具有广阔的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3fb/7237551/3550a9808ae2/11671_2020_3293_Fig1_HTML.jpg

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