X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs

• DOI: 10.2147/ijn.s164967
• Publication Date: 2018-06-18T22:48:55Z
• Authors: Sandhya Clement; Wenjie Chen; Wei Deng; Ewa M Goldys
• Keywords: Medicine (General); folic acid targeting; Image Processing; 32 Biomedical and Clinical Sciences; Biocompatible Materials; anzsrc-for: 4018 Nanotechnology; Photodynamic therapy; Computer-Assisted; Polylactic Acid-Polyglycolic Acid Copolymer; International Journal of Nanomedicine; anzsrc-for: 1115 Pharmacology and Pharmaceutical Sciences; Image Processing, Computer-Assisted; Nanotechnology; Cancer; X-ray PDT; Original Research; 0303 health sciences; Tumor; Photosensitizing Agents; Singlet Oxygen; singlet oxygen generation; anzsrc-for: 1007 Nanotechnology; 3. Good health; photodynamic therapy; anzsrc-for: 0601 Biochemistry and Cell Biology; 3206 Medical Biotechnology; Porphyrins; anzsrc-for: 4003 Biomedical engineering; Cell Survival; Static Electricity; 610; Bioengineering; anzsrc-for: 3206 Medical Biotechnology; Cell Line; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; R5-920; Folic Acid; Cell Line, Tumor; Singlet oxygen generation; Humans; Lactic Acid; Particle Size; X-Rays; Verteporfin; Photochemotherapy; PLGA nanoparticles; Radiation Oncology; Nanoparticles; Polyglycolic Acid

The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors.To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated.Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue.The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.