PDF(Pubmed)
Abstract：
Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.
摘要：
声动力疗法（SDT），一种具有深层组织渗透能力的癌症治疗策略，近年来受到了广泛的关注。具有肿瘤特异性疗效的内在特征的声敏剂，肿瘤微环境（TME）调节和肿瘤诊断的需求很高。在这里，无定形CoBiMn-层状双氢氧化物（a-CoBiMn-LDH）纳米颗粒被提出作为多功能超声敏化剂，以触发用于超声（US）成像引导的SDT的活性氧（ROS）生成。通过简单的酸处理蚀刻水热合成的CoBiMn-LDH纳米颗粒以获得具有丰富缺陷的a-CoBiMn-LDH纳米颗粒。a-CoBiMn-LDH纳米颗粒在US辐照时产生更多的ROS，达到晶体CoBiMn-LDH纳米颗粒和商业TiO2超声敏化剂的水平~3.3倍和~8.2倍，分别。这种优异的US触发的ROS产生性能可归因于缺陷诱导的窄带隙和促进的电子和空穴(e-/h+)分离。更重要的是,Mn4+的存在使a-CoBiMn-LDH纳米颗粒能够通过将H2O2分解为O2来调节TME，以缓解缺氧和US成像，并消耗谷胱甘肽（GSH）以防止ROS清除。生物学机制分析表明，聚乙二醇修饰的a-CoBiMn-LDH纳米颗粒可以作为多功能的超声增敏剂，通过激活p53，凋亡，在US照射下有效杀伤癌细胞，消除体内肿瘤，和氧化磷酸化相关的信号通路。
