Intrinsic, Cancer Cell-Selective Toxicity of Organic Photothermal Nanoagent: A Simple Formulation for Combined Photothermal Chemotherapy of Cancer
Intrinsic, Cancer Cell-Selective Toxicity of Organic Photothermal Nanoagent: A Simple Formulation for Combined Photothermal Chemotherapy of Cancer
复制标题
有机光热纳米剂的内在癌细胞选择性毒性：癌症联合光热化疗的简单配方
DOI：
10.1021/acsami.8b07801
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发表时间：
2018-08-08
影响因子：
9.5
通讯作者：
Zhang, Liming
中科院分区：
文献类型：
--
作者：
Lu, Zhuoxuan;Huang, Feng-Ying;Zhang, Liming
纳米光热疗法（PTT）联合化疗已被认为是治疗癌症的有效策略。然而，化疗药物往往会引起严重的副作用。本文开发了一种新型PTT纳米剂（Cy5.5-MSA-G250），具有意想不到的内在肿瘤选择性细胞毒性。将小鼠血清白蛋白（MSA）和考马斯亮蓝（G250）混合，然后与菁氨酸5.5 （Cy5.5）偶联，制备Cy5.5-MSA-G250纳米颗粒（NPs）。正如预期的那样，Cy5.5-MSA-G250 NPs可以通过PTT在体外和体内有效地杀死癌细胞。同时，我们偶然发现Cy5.5-MSA-G250对肿瘤细胞具有固有的特异性细胞毒性，而对正常细胞没有特异性细胞毒性。此外，Cy5.5-MSA-G250的肿瘤特异性细胞毒性比FDA批准的抗癌药物阿糖胞苷强得多。体内实验也证明Cy5.5-MSA-G250 NPs能有效清除残留肿瘤细胞，防止肿瘤转移。进一步研究表明，选择性诱导肿瘤细胞G1周期阻滞和抑制肿瘤细胞DNA复制可能是Cy5.5-MSA-G250 NPs具有肿瘤细胞选择性细胞毒性的可能机制。此外，直接可视化、低系统毒性、良好的生物降解和高效的体内排泄，进一步使Cy5.5-MSA-G250 NPs具有在体内应用的吸引力。综上所述，Cy5.5-MSA-G250 NPs被证明是一个有前景的联合光热化疗平台。
Nano-agent-mediated photothermal therapy (PTT) combined with chemotherapy has been proposed as an effective strategy against cancer. However, chemotherapeutic agents often cause serious side effects. Herein, a novel PTT nanoagent (Cy5.5-MSA-G250) with unanticipated intrinsic tumor-selective cytotoxicity is developed. The Cy5.5-MSA-G250 nanoparticles (NPs) are created by mixing mouse serum albumin (MSA) and coomassie brilliant blue (G250) and then conjugated with cyanine 5.5 (Cy5.5). As expected, Cy5.5-MSA-G250 NPs can efficiently kill cancer cells in vitro and in vivo by PTT. Meanwhile, we accidentally discover that Cy5.5-MSA-G250 have intrinsic specific cytotoxicity against tumor cells but not against normal cells. Moreover, the tumor-specific cytotoxicity of Cy5.5-MSA-G250 is much stronger than that of cytarabine, an FDA approved anticancer drug. In vivo experiments also prove that Cy5.5-MSA-G250 NPs can effectively eliminate residual tumor cells and prevent metastasis. Further study indicates that selective induction of G1 cell cycle arrest and inhibition of DNA duplication in tumor cells may be the possible mechanism of the tumor cell-selective cytotoxicity of Cy5.5-MSA-G250 NPs. In addition, direct visualization, low systematic toxicity, good biodegradation, and efficient body excretion further make Cy5.5-MSA-G250 NPs attractive for in vivo applications. Taken together, Cy5.5-MSA-G250 NPs are proven to be a promising platform for combined photothermal chemotherapy.