Department of Oncology, University of Alberta, 11560 University Avenue NW, Edmonton, AB T6G 1Z2, Canada.
Department of Chemical and Materials Engineering, University of Alberta, 9211-116 Street NW, Edmonton, AB T6G 2G6, Canada.
Acta Biomater. 2020 Nov;117:335-348. doi: 10.1016/j.actbio.2020.09.029. Epub 2020 Sep 19.
Photodynamic Therapy (PDT) is an effective treatment modality for cancers, with Protoporphyrin IX (PPIX)-based PDT being the most widely used to treat cancers in patients. However, PDT is limited to superficial, thin (few mm in depth) lesions that can be accessed by visible wavelength light. Interstitial light-delivery strategies have been developed to treat deep-seated lesions (i.e. prostate cancer). The most promising of these are X-ray-induced scintillation nanoparticles, which have shown potential benefits for PDT of deep-seated tumors. Herein, the design and use of a new nanoscintillator-based radiation-activated PDT (radioPDT) system is investigated in the treatment of deep-seated tumors. Poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanospheres were loaded with a scintillator (LaF:Ce) and photosensitizer (PPIX) to effect radioPDT. UV-Vis spectroscopy and electron microscopy studies demonstrated efficient encapsulation of nanoscintillators and PPIX (>90% efficiency) into the PEG-PLGA nanospheres. The nanoparticles were uniform in size and approximately 100 nm in diameter. They were highly stable and functional for up to 24 h under physiological conditions and demonstrated slow release kinetics. In vitro and in vivo toxicity studies showed no appreciable drug toxicity to human skin fibroblast (GM38), prostate cancer cells (PC3), and to C57/BL mice. Cell uptake studies demonstrated accumulation of the nanoparticles in the cytoplasm of PC3 cells. When activated, fluorescent resonant energy transfer (FRET) was evident via fluorescent spectroscopy and singlet oxygen yield. Determination of stability revealed that the nanoparticles were stable for up to 4 weeks. The nanoparticle production was scaled-up with no change in properties. This nanoparticle represents a unique, optimally designed therapeutic and diagnostic agent (theranostic) agent for radioPDT with characteristics capable of potentially augmenting radiotherapy for deep-seated tumors and integrating into current cancer radiotherapy.
光动力疗法（PDT）是一种有效的癌症治疗方法，以原卟啉 IX（PPIX）为基础的 PDT 是最广泛用于治疗患者癌症的方法。然而，PDT 仅限于可以通过可见波长光进入的浅表、薄（几毫米深）病变。已经开发了间质光输送策略来治疗深部病变（即前列腺癌）。其中最有前途的是 X 射线诱导闪烁纳米粒子，它们已显示出对深部肿瘤 PDT 的潜在益处。在此，研究了一种新的基于纳米闪烁体的辐射激活光动力疗法（radioPDT）系统在深部肿瘤治疗中的设计和应用。聚乙二醇甲基醚嵌段-聚（乳酸-co-乙醇酸）（PEG-PLGA）纳米球负载闪烁体（LaF：Ce）和光敏剂（PPIX）以实现 radioPDT。紫外-可见光谱和电子显微镜研究表明，纳米闪烁体和 PPIX（>90%效率）有效地封装在 PEG-PLGA 纳米球中。纳米粒子大小均匀，直径约为 100nm。它们在生理条件下高度稳定且功能长达 24 小时，并表现出缓慢的释放动力学。体外和体内毒性研究表明，对人皮肤成纤维细胞（GM38）、前列腺癌细胞（PC3）和 C57/BL 小鼠没有明显的药物毒性。细胞摄取研究表明纳米粒子在 PC3 细胞的细胞质中积累。当被激活时，通过荧光光谱和单线态氧产率可以明显看出荧光共振能量转移（FRET）。稳定性测定表明，纳米粒子在长达 4 周的时间内稳定。纳米颗粒的产量增加而没有改变性质。该纳米颗粒代表了一种独特的、经过优化设计的治疗和诊断剂（治疗剂），用于 radioPDT，具有潜在增强深部肿瘤放射治疗和整合到当前癌症放射治疗的特性。
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