Fullerenol-Cytotoxic Conjugates for Cancer Chemotherapy
Fullerenol-Cytotoxic Conjugates for Cancer Chemotherapy
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DOI：
10.1021/nn900318y
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发表时间：
2009-09-01
期刊：
影响因子：
17.1
通讯作者：
Sengupta, Shiladitya
中科院分区：
文献类型：
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作者：
Chaudhuri, Padmaparna;Paraskar, Abhimanyu;Sengupta, Shiladitya
在本研究中，我们报告了新的应用多羟基富勒烯（富勒醇）在癌症药物输送。用于在富勒烯笼上产生多个羟基的简易合成程序除了赋予亲水性之外还提供了高药物负载的范围。多柔比星，一线癌症化疗药物，通过氨基甲酸酯连接体与富勒烯醇缀合，实现了富勒烯负载效率。发现药物-富勒醇缀合物在磷酸盐缓冲盐水中相对稳定，但当与肿瘤细胞裂解物孵育时暂时释放活性药物。富勒醇-阿霉素缀合物通过G2-M细胞周期阻滞抑制体外癌细胞系的增殖，导致凋亡。此外，在体内鼠肿瘤模型中，富勒烯醇-多柔比星表现出与游离药物相当的抗肿瘤功效，而没有游离多柔比星的全身毒性。此外，我们证明富勒醇平台可以扩展到其他化疗药物，如微水溶性顺铂，并可以作为一种新的范例出现在癌症的管理。
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.