Wang Dan, Zhao Jianyang, Mulder Roger J, Ratcliffe Julian, Wang Chunru, Wu Bo, Wang Jinquan, Hao Xiaojuan
Guangdong Pharmaceutical University Guangzhou Guangdong China.
Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO) Clayton Victoria Australia.
Smart Med. 2023 Dec 20;2(4):e20230033. doi: 10.1002/SMMD.20230033. eCollection 2023 Nov.
Fullerenes are a class of carbon nanomaterials that find a wide range of applications in biomedical fields, especially for photodynamic cancer therapy because of its photosensitive effect. However, hydrophobic fullerenes can only be dispersed in organic solvents which hinders their biomedical applications. Here, we report a facile method to prepare highly water-dispersible fullerene (C)-polymer nanoparticles with hydrodynamic sizes of 50-70 nm. Hydrophilic random copolymers containing different ratios of polyethylene glycol methyl ether methacrylate and 2-aminoethylmethacrylamide were synthesized for conjugating with C molecules through efficient nucleophilic Michael addition reaction between amine groups from hydrophilic polymer and carbon-carbon double bonds from C. As a result, the amphiphilic C-polymer conjugates could be well dispersed and nano-assembled in water with a C concentration as high as 7.8 mg/mL, demonstrating a significant improvement for the solubility of C in an aqueous system. Owing to the high C content, the C-polymer nanoparticles showed a strong photodynamic therapy effect on human lung cancer cells (A549) under light irradiation (450 nm) in both 2D cell culture and 3D spheroid culture, while demonstrating ignorable cytotoxicity under dark. This highly efficient and convenient method to prepare water-dispersible C-polymer conjugates may have a great impact on the future biomedical applications of fullerenes.
富勒烯是一类碳纳米材料，因其光敏效应在生物医学领域有广泛应用，尤其适用于光动力癌症治疗。然而，疏水性富勒烯只能分散在有机溶剂中，这阻碍了它们在生物医学领域的应用。在此，我们报道了一种简便方法来制备水动力尺寸为50 - 70纳米的高度水分散性富勒烯（C）-聚合物纳米颗粒。合成了含有不同比例聚乙二醇甲基醚甲基丙烯酸酯和2-氨基乙基甲基丙烯酸酰胺的亲水性无规共聚物，通过亲水性聚合物中的胺基与C中的碳 - 碳双键之间的高效亲核迈克尔加成反应与C分子共轭。结果，两亲性C - 聚合物共轭物能够在水中良好分散并纳米组装，C浓度高达7.8毫克/毫升，表明C在水体系中的溶解度有显著提高。由于高C含量，C - 聚合物纳米颗粒在二维细胞培养和三维球体培养中，在光照射（450纳米）下对人肺癌细胞（A549）显示出强烈的光动力治疗效果，而在黑暗条件下细胞毒性可忽略不计。这种制备水分散性C - 聚合物共轭物的高效便捷方法可能会对富勒烯未来的生物医学应用产生重大影响。
