Xiong Wei, Guo Zhengdong, Zeng Baoyan, Wang Teng, Zeng Xiaowei, Cao Wei, Lian Daizheng
Department of Plastic and Burn Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.
Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
Front Bioeng Biotechnol. 2022 Feb 17;10:847901. doi: 10.3389/fbioe.2022.847901. eCollection 2022.
Dacarbazine (DTIC) dominates chemotherapy for malignant melanoma (MM). However, the hydrophobicity, photosensitivity, instability, and toxicity to normal cells of DTIC limit its efficacy in treating MM. In the present study, we constructed star-shaped block polymers nanoparticles (NPs) based on Cholic acid -poly (lactide--glycolide)--polyethylene glycol (CA-PLGA--PEG) for DTIC encapsulation and MM targeted therapy. DTIC-loaded CA-PLGA--PEG NPs (DTIC-NPs) were employed to increase the drug loading and achieve control release of DTIC, followed by further modification with nucleic acid aptamer AS1411 (DTIC-NPs-Apt), which played an important role for active targeted therapy of MM. , DTIC-NPs-Apt showed good pH-responsive release and the strongest cytotoxicity to A875 cells compared with DTIC-NPs and free DTIC. results demonstrated that the versatile DTIC-NPs-Apt can actively target the site of MM and exhibited excellent anti-tumor effects with no obvious side effects. Overall, this research provided multi-functional NPs, which endow a new option for the treatment of MM.
达卡巴嗪(DTIC)在恶性黑色素瘤(MM)的化疗中占据主导地位。然而,DTIC的疏水性、光敏性、不稳定性以及对正常细胞的毒性限制了其在治疗MM方面的疗效。在本研究中,我们构建了基于胆酸-聚(丙交酯-乙交酯)-聚乙二醇(CA-PLGA-PEG)的星形嵌段聚合物纳米颗粒(NPs)用于DTIC包封和MM靶向治疗。负载DTIC的CA-PLGA-PEG NPs(DTIC-NPs)用于增加药物负载量并实现DTIC的控释,随后用核酸适配体AS1411进一步修饰(DTIC-NPs-Apt),其在MM的主动靶向治疗中发挥重要作用。与DTIC-NPs和游离DTIC相比,DTIC-NPs-Apt表现出良好的pH响应释放以及对A875细胞最强的细胞毒性。结果表明,多功能的DTIC-NPs-Apt可以主动靶向MM部位并展现出优异的抗肿瘤效果且无明显副作用。总体而言,本研究提供了多功能NPs,为MM的治疗赋予了新的选择。