Activating TiO2 Nanoparticles: Gallium-68 Serves as a High-Yield Photon Emitter for Cerenkov-Induced Photodynamic Therapy
Activating TiO2 Nanoparticles: Gallium-68 Serves as a High-Yield Photon Emitter for Cerenkov-Induced Photodynamic Therapy
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激活 TiO2 纳米粒子：Gallium-68 作为切伦科夫诱导光动力疗法的高产光子发射器。
DOI：
10.1021/acsami.7b17902
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发表时间：
2018-02-14
影响因子：
9.5
通讯作者：
Liu, Zhibo
中科院分区：
文献类型：
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作者：
Duan, Dongban;Liu, Hui;Liu, Zhibo
经典的光动力疗法（PDT）需要外部光源来激活光敏剂以治疗癌症。然而，光在组织中的穿透有限一直是PDT治疗深部组织恶性肿瘤的长期挑战。最近，由放射性示踪剂如氟脱氧葡萄糖（¹⁸F - FDG）发出的切伦科夫辐射（CR）已成为一种有替代潜力的内部光源。然而，氟 - 18（F - 18）平均每次衰变仅释放1.3个光子；因此，由于其切伦科夫产率低，为了获得治疗效果，F - 18的注射剂量比通常要多10 - 30倍。镓 - 68（Ga - 68）是一种良好的CR源，因为它可从发生器方便地获取，且切伦科夫产率高30倍。在此，我们首次报道使用Ga - 68作为CR源来激活葡聚糖修饰的二氧化钛纳米粒子（D - TiO₂ NPs）以进行CR诱导的PDT。与¹⁸F - FDG相比，镓 - 68标记的牛血清白蛋白（⁶⁸Ga - BSA）抑制了4T1细胞的生长，并对肿瘤细胞表现出明显更强的DNA损伤。体内研究表明，当荷瘤小鼠接受D - TiO₂ NPs和⁶⁸Ga - BSA联合治疗时，肿瘤生长几乎完全被抑制。这项研究证明，在体外和体内，Ga - 68用于PDT比F - 18是一种更有效的放射性核素，提供了一种有前景的策略，即使用诊断剂量的放射性在不使用任何外部光源的情况下实现与深度无关的癌症治疗。
The classical photodynamic therapy (PDT) requires external light to activate photosensitizers for cancer treatment. However, limited tissue penetration of light has been a long-standing challenge for PDT to cure malignant tumors in deep tissues. Recently, Cerenkov radiation (CR) emitted by radiotracers such as 18F-fluorodeoxyglucose (18F-FDG) has become an alternative and promising internal light source. Nevertheless, fluorine-18 (F-18) only releases 1.3 photons per decay in average; consequently, injection dose of F-18 goes beyond 10-30 times more than usual to acquire therapeutic efficacy because of its low Cerenkov productivity. Gallium-68 (Ga-68) is a favorable CR source owing to its ready availability from generator and 30-time higher Cerenkov productivity. Herein, we report, for the first time, the use of Ga-68 as a CR source to activate dextran-modified TiO2 nanoparticles (D-TiO2 NPs) for CR-induced PDT. Compared with 18F-FDG, 68Ga-labeled bovine serum albumin (68Ga-BSA) inhibited the growth of 4T1 cells and exhibited significantly stronger DNA damage to tumor cells. In vivo studies showed that the tumor growth was almost completely inhibited when tumor-bearing mice were treated with a combination of D-TiO2 NPs and 68Ga-BSA. This study proved that Ga-68 is a more potent radionuclide for PDT than F-18 both in vitro and in vivo offered a promising strategy of using a diagnostic dose of radioactivity to achieve depth-independent cancer therapy without using any external light source.