Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer Therapy.
Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer Therapy.
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DOI：
10.1021/acs.nanolett.7b05292
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发表时间：
2018-01
期刊：
影响因子：
10.8
通讯作者：
Xu Zhen;Chen Xie;Yuyan Jiang;Xiangzhao Ai;B. Xing;Kanyi Pu
中科院分区：
文献类型：
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作者：
Xu Zhen;Chen Xie;Yuyan Jiang;Xiangzhao Ai;B. Xing;Kanyi Pu
纳米医学在癌症治疗中已经显示出成功，但是大多数纳米医学的药理学作用通常对癌细胞是非特异性的，因为利用了从内部细胞器诱导细胞凋亡的治疗剂。我们在此报道了半导体光热纳米激动剂的发展，其可以远程和特异性地从细胞膜启动癌细胞的凋亡。有机纳米激动剂包含半导体聚合物纳米颗粒（SPN）和辣椒素（Cap），分别作为光热响应性纳米载体和用于激活瞬时受体电位阳离子通道亚家族V成员1（TRPV 1）的激动剂。在以秒为时间尺度的多次NIR激光照射下，纳米激动剂可以重复和局部释放Cap以多次激活细胞膜上的TRPV 1通道;累积效应是线粒体中离子的过度流入，随后诱导TRPV 1阳性癌细胞的细胞凋亡。TRPV 1通道的多次瞬时激活对于在体外和体内诱导这样的细胞死亡是必不可少的，因为游离Cap和简单Cap包封的纳米颗粒都不能这样做。光热触发的释放还确保了TRPV 1激动剂在肿瘤部位的高局部浓度，允许以低全身给药剂量进行特异性癌细胞治疗。因此，我们的研究表明，第一个例子的离子通道特异性和远程控制的药物输送系统的癌细胞治疗。
Nanomedicine have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser irradiation at the time scale of seconds, the nanoagonists can repeatedly and locally release Cap to multiply activate TRPV1 channels on the cellular membrane; the cumulative effect is the overinflux of ions in mitochondria followed by the induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple transient activation of TRPV1 channels is essential to induce such a cell death both in vitro and in vivo because both free Cap and simple Cap-encapsulated nanoparticles fail to do so. The photothermally triggered release also ensures a high local concentration of the TRPV1 agonist at tumor site, permitting specific cancer cell therapy at a low systemic administration dosage. Our study thus demonstrates the first example of ion-channel-specific and remote-controlled drug-delivery system for cancer cell therapy.