Ling Junhong, Cai Yingying, Feng Haozhan, Liu Zhen, Ouyang Xiao-Kun
School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
Pharmaceutics. 2024 Apr 7;16(4):512. doi: 10.3390/pharmaceutics16040512.
Disulfiram (DSF) degrades to diethyldithiocarbamate (DTC) in vivo and coordinates with copper ions to form CuET, which has higher antitumor activity. In this study, DSF@CuMSN-PDA nanoparticles were prepared using mesoporous silica with copper ions, DSF as a carrier, and polydopamine (PDA) as a gate system. The nanoparticles selectively released CuET into tumor tissue by taking advantage of the tumor microenvironment, where PDA could be degraded. The release ratio reached 79.17% at pH 5.0, indicating pH-responsive drug release from the nanoparticles. The PDA-gated system provided the nanoparticles with unique photothermal conversion performance and significantly improved antitumor efficiency. In vivo, antitumor experiments showed that the designed DSF@CuMSN-PDA nanoparticles combined with near-infrared light (808 nm, 1 W/cm) irradiation effectively inhibited tumor growth in HCT116 cells by harnessing the combined potential of chemotherapy and photothermal therapy; a synergistic effect was achieved. Taken together, these results suggest that the designed DSF@CuMSN-PDA construct can be employed as a promising candidate for combined chemo-photothermal therapy.
双硫仑（DSF）在体内降解为二乙基二硫代氨基甲酸盐（DTC），并与铜离子配位形成具有更高抗肿瘤活性的CuET。在本研究中，以含铜离子的介孔二氧化硅为载体、DSF为原料，并以聚多巴胺（PDA）作为门控系统，制备了DSF@CuMSN-PDA纳米颗粒。该纳米颗粒利用肿瘤微环境（其中PDA可被降解）将CuET选择性释放到肿瘤组织中。在pH 5.0时释放率达到79.17%，表明纳米颗粒具有pH响应性药物释放特性。PDA门控系统赋予纳米颗粒独特的光热转换性能，并显著提高了抗肿瘤效率。在体内抗肿瘤实验中，设计的DSF@CuMSN-PDA纳米颗粒结合近红外光（808 nm，1 W/cm）照射，通过利用化疗和光热疗法的联合潜力，有效抑制了HCT116细胞中的肿瘤生长；实现了协同效应。综上所述，这些结果表明，所设计的DSF@CuMSN-PDA构建体可作为联合化疗-光热疗法的有前景的候选物。
