Institute of Functional Nano & Soft Materials, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University , Suzhou, Jiangsu 215123, China.
University of Wisconsin Carbone Cancer Centre , Madison, Wisconsin United States.
ACS Appl Mater Interfaces. 2016 Oct 12;8(40):26630-26637. doi: 10.1021/acsami.6b10255. Epub 2016 Sep 30.
Traditional photodynamic therapy (PDT) requires external light to activate photosensitizers for therapeutic purposes. However, the limited tissue penetration of light is still a major challenge for this method. To overcome this limitation, we report an optimized system that uses Cerenkov radiation for PDT by using radionuclides to activate a well-known photosensitizer (chlorin e6, Ce6). By taking advantage of hollow mesoporous silica nanoparticles (HMSNs) that can intrinsically radiolabel an oxophilic zirconium-89 (Zr, t = 78.4 h) radionuclide, as well as possess great drug loading capacity, Ce6 can be activated by Cerenkov radiation from Zr in the same nanoconstruct. In vitro cell viability experiments demonstrated dose-dependent cell deconstruction as a function of the concentration of Ce6 and Zr. In vivo studies show inhibition of tumor growth when mice were subcutaneously injected with [Zr]HMSN-Ce6, and histological analysis of the tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use an internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications.
传统的光动力疗法（PDT）需要外部光来激活光敏剂以达到治疗目的。然而，光的有限组织穿透性仍然是该方法的一个主要挑战。为了克服这一限制，我们报告了一种优化的系统，该系统利用放射性核素激活一种众所周知的光敏剂（氯乙酮，Ce6）来利用切伦科夫辐射进行 PDT。利用可以内在放射性标记亲氧锆-89（Zr，t = 78.4 h）放射性核素的中空介孔硅纳米粒子（HMSNs），以及具有巨大的药物负载能力，Ce6 可以被 Zr 在同一纳米结构中产生的切伦科夫辐射激活。体外细胞活力实验表明，Ce6 和 Zr 的浓度依赖性细胞解构与浓度有关。体内研究表明，当小鼠皮下注射 [Zr]HMSN-Ce6 时，肿瘤生长受到抑制，肿瘤组织的组织学分析表明肿瘤组织受损，这意味着活性氧物质介导了破坏。这项研究为利用内部辐射源实现深部肿瘤治疗提供了一种方法，而无需使用任何外部光源，以便将来应用。
