Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.
Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent.
复制标题
血液触发的铂纳米粒子的产生起到抗癌剂的作用。
DOI：
10.1038/s41467-019-14131-z
复制
发表时间：
2020
影响因子：
16.6
通讯作者：
Zhang Gen
中科院分区：
文献类型：
--
作者：
Zeng Xin;Sun Jie;Li Suping;Shi Jiyun;Gao Han;Sun Leong Wei;Wu Yiqi;Li Minghui;Liu Chengxin;Li Ping;Kong Jing;Wu Yi-Zhou;Nie Guangjun;Fu Yuming;Zhang Gen
自20世纪60年代发现金属纳米颗粒（NPs）以来，未知的毒性，成本和人类研究的伦理障碍阻碍了这些NPs的临床应用。在这项工作中，我们证明，铂纳米粒子与蛋白质冠在体内产生的人血液中，当患者用顺铂治疗。这些自组装的Pt纳米颗粒迅速形成，在肿瘤中积累，并在体内停留很长一段时间。此外，铂纳米颗粒可安全用于人类，并可作为抗癌剂，通过消耗细胞内谷胱甘肽和激活细胞凋亡来抑制化疗抗性肿瘤的生长。当铂纳米颗粒在体外装载化疗药物柔红霉素时，肿瘤抑制活性大大增强，并且该制剂即使在柔红霉素耐药模型中也有效。这些体内产生的金属纳米颗粒代表了用于化疗抗性肿瘤治疗的生物相容性药物递送平台。
Since the discovery of metal nanoparticles (NPs) in the 1960s, unknown toxicity, cost and the ethical hurdles of research in humans have hindered the translation of these NPs to clinical use. In this work, we demonstrate that Pt NPs with protein coronas are generated in vivo in human blood when a patient is treated with cisplatin. These self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period of time. Additionally, the Pt NPs are safe for use in humans and can act as anti-cancer agents to inhibit chemotherapy-resistant tumor growth by consuming intracellular glutathione and activating apoptosis. The tumor inhibitory activity is greatly amplified when the Pt NPs are loaded in vitro with the chemotherapeutic drug, daunorubicin, and the formulation is effective even in daunorubicin-resistant models. These in vivo-generated metal NPs represent a biocompatible drug delivery platform for chemotherapy resistant tumor treatment.