State Key Laboratory of Rare Earth Resource Utilization , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022 , People's Republic of China.
University of Science and Technology of China , Hefei 230026 , People's Republic of China.
Nano Lett. 2019 Jun 12;19(6):4134-4145. doi: 10.1021/acs.nanolett.9b01595. Epub 2019 May 17.
As a noninvasive treatment modality, ultrasound (US)-triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (HO) to produce O that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.
作为一种非侵入性的治疗方式，超声（US）触发声动力学疗法（SDT）显示出广泛而有前途的应用，可克服传统光动力学疗法（PDT）在治疗癌症方面的缺点。然而，在没有氧气（O）辅助的情况下，SDT 的疗效仍然不尽如人意。此外，在基于 SDT 的协同治疗方式方面，还有很大的探索空间。在此，合理设计并成功合成了一种由中空半导体 CuS 和贵金属 Pt 组成的新型 Pt-CuS 双面体。中空 CuS 具有较大的内腔，可用于装载声敏剂分子（四（4-氨基苯基）卟啉，TAPP）以实现 SDT。此外，Pt 的沉积不仅由于局部电场增强的影响，与 CuS 纳米颗粒（NPs）相比增强了光热性能，而且还具有纳米酶活性，可催化分解内源性过表达的过氧化氢（HO）产生 O，从而克服肿瘤缺氧并增强 SDT 诱导的高毒性活性氧（ROS）产生，以有效促进癌细胞凋亡。重要的是，808nm 激光照射下 Pt-CuS 产生的热量可以加速 Pt 的催化活性并提高 O 水平，从而进一步提高 SDT 的疗效。有趣的是，Janus 周围涂覆的热敏共聚物可以作为智能开关来调节 Pt 的催化能力并控制 TAPP 的释放，这对调节治疗效果有显著影响。协同催化增强的 SDT 效率和高热光效应几乎实现了完全的肿瘤切除，没有明显的复发，同时表现出高度的治疗生物安全性。此外，高光学吸收率使合成的 Pt-CuS 双面体能够进行光声（PA）成像和近红外热成像。这项工作开发了一种多功能治疗策略的通用纳米平台，并通过合理设计其结构拓宽了其生物应用。
