Chaudhuri Padmaparna, Paraskar Abhimanyu, Soni Shivani, Mashelkar Raghunath A, Sengupta Shiladitya
Laboratory of Nanomedicine, HST Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, USA.
ACS Nano. 2009 Sep 22;3(9):2505-14. doi: 10.1021/nn900318y.
In the present study, we report the novel application of polyhydroxylated fullerenes (fullerenols) in cancer drug delivery. The facile synthetic procedure for generating multiple hydroxyl groups on the fullerene cage offers scope for high drug loading in addition to conferring hydrophilicity. Doxorubicin, a first line cancer chemotherapeutic, was conjugated to fullerenols through a carbamate linker, achieving ultrahigh loading efficiency. The drug-fullerenol conjugate was found to be relatively stable in phosphate buffer saline but temporally released the active drug when incubated with tumor cell lysate. The fullerenol-doxorubicin conjugate suppressed the proliferation of cancer cell-lines in vitro through a G2-M cell cycle block, resulting in apoptosis. Furthermore, in an in vivo murine tumor model, fullerenol-doxorubicin exhibited comparable antitumor efficacy as free drug without the systemic toxicity of free doxorubicin. Additionally, we demonstrate that the fullerenol platform can be extended to other chemotherapeutic agents, such as the slightly water-soluble cisplatin, and can emerge as a new paradigm in the management of cancer.
在本研究中，我们报道了多羟基化富勒烯（富勒醇）在癌症药物递送中的新应用。在富勒烯笼上生成多个羟基的简便合成方法，除了赋予亲水性外，还为高载药量提供了空间。阿霉素是一线癌症化疗药物，通过氨基甲酸酯连接体与富勒醇共轭，实现了超高的载药效率。发现药物 - 富勒醇共轭物在磷酸盐缓冲盐水中相对稳定，但与肿瘤细胞裂解物孵育时会定时释放活性药物。富勒醇 - 阿霉素共轭物通过G2 - M细胞周期阻滞在体外抑制癌细胞系的增殖，导致细胞凋亡。此外，在体内小鼠肿瘤模型中，富勒醇 - 阿霉素表现出与游离药物相当的抗肿瘤功效，且没有游离阿霉素的全身毒性。此外，我们证明富勒醇平台可以扩展到其他化疗药物，如微溶于水的顺铂，并可成为癌症治疗的新范例。
