One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-Guided Trimodal Therapy
One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-Guided Trimodal Therapy
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DOI：
10.1002/adfm.201603394
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发表时间：
2016-12-20
影响因子：
19
通讯作者：
Yogo, Toshinobu
中科院分区：
文献类型：
--
作者：
Hayashi, Koichiro;Maruhashi, Takuma;Yogo, Toshinobu
利用外源性和内源性刺激响应性可降解纳米粒作为药物载体可以改善药物递送系统（DDS）。使用中空纳米颗粒可促进降解，DDS与光动力疗法（PDT）和光热疗法（PTT）的组合可增强治疗的抗癌效果。在这里，提出了一种一锅法合成抗癌药物（多柔比星[DOX]）和含有光敏剂的中空混合纳米颗粒（HNP）的方法，该纳米颗粒具有响应于外源性（光）和内源性（细胞内谷胱甘肽[GSH]）刺激而形成的二硫化物和硅氧烷框架。中空HNP在近红外窗口内发射荧光，并允许通过荧光成像检测体内肿瘤。此外，HNP框架内的二硫化物被细胞内GSH切割，使HNP变形。光照射促进GSH渗透到HNP框架中并导致HNP的塌陷。结果，DOX从中空HNP释放。此外，中空HNP响应于光产生单线态氧（O-1（2））和热;因此，肿瘤的荧光成像与由DDS、PDT和PTT组成的三模式疗法组合是可行的，导致上级治疗功效。因此，这种方法可能在未来的成像和治疗中有几个应用。
Exploiting exogenous and endogenous stimulus-responsive degradable nanoparticles as drug carriers can improve drug delivery systems (DDSs). The use of hollow nanoparticles may facilitate degradation, and combination of DDS with photodynamic therapy (PDT) and photothermal therapy (PTT) may enhance the anticancer effects of treatments. Here, a one-pot synthetic method is presented for an anticancer drug (doxorubicin [DOX]) and photosensitizer-containing hollow hybrid nanoparticles (HNPs) with a disulfide and siloxane framework formed in response to exogenous (light) and endogenous (intracellular glutathione [GSH]) stimuli. The hollow HNPs emit fluorescence within the near-infrared window and allow for the detection of tumors in vivo by fluorescence imaging. Furthermore, the disulfides within the HNP framework are cleaved by intracellular GSH, deforming the HNPs. Light irradiation facilitates penetration of GSH into the HNP framework and leads to the collapse of the HNPs. As a result, DOX is released from the hollow HNPs. Additionally, the hollow HNPs generate singlet oxygen (O-1(2)) and heat in response to light; thus, fluorescence imaging of tumors combined with trimodal therapy consisting of DDS, PDT, and PTT is feasible, resulting in superior therapeutic efficacy. Thus, this method may have several applications in imaging and therapeutics in the future.