PEG-PLGA nanospheres loaded with nanoscintillators and photosensitizers for radiation-activated photodynamic therapy. (November 2020)

• Record Type: Journal Article
• Authors: Dinakaran, Deepak; Sengupta, Jayeeta; Pink, Desmond; Raturi, Arun; Chen, Hua; Usmani, Nawaid; Kumar, Piyush; Lewis, John D; Narain, Ravin; Moore, Ronald B
• Is Part Of: Acta biomaterialia. Volume 117(2020)
• Page Start: 335
• Page End: 348
• Publication Date: 2020-11
• Subjects: Photodynamic therapy -- Nanoscintillators -- Protoporphyrin IX -- Prostate cancer -- RadioPDT -- Theranostic; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2020.09.029
• Languages: English
• ISSNs: 1742-7061

Abstract

Abstract: 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 (LaF3 :Ce 3+ ) 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. Graphical abstract: Image, graphical abstract