Photodynamic therapy (PDT) is a clinically approved method for the treatment of cancer by using singlet oxygen, a highly reactive oxygen generated from a photosensitizer drug upon photoactivation. Limited light penetration depth into the tissue means that PDT is unsuitable for deep tissue cancer treatments. To overcome this issue, we developed a dual PDT system where poly (D, L-lactide-co-glycolide) (PLGA) polymeric nanoparticles incorporating a photosensitizer, verteporfin, can be triggered to generate cytotoxic singlet oxygen by both red light at 690 nm and by 6 MeV X-ray radiation. The X-ray radiation used in this study allows this system to break through the PDT depth barrier, due to excellent penetration of 6 MeV X-ray radiation though biological tissue. In addition, the conjugation of the nanoparticles with folic acid moieties has enabled specific targeting of HCT116 cancer cells which overexpress the folate receptors. Physiochemical characterization of PLGA nanoparticles, such as size distribution, zeta potential, morphology and in-vitro release of verteporfin was also carried out. These studies indicate that improved tumour cell killing effects can be achieved with nanoparticles triggered by 690 nm as well as 6 MeV radiation, compared with nanoparticles alone. We attribute the X-ray induced singlet oxygen generation from the photosensitizer verteprofin to photoexcitation by Cerenkov radiation and/or chemical reaction facilitated by energetic secondary electrons produced in the tissue. This effect offers the possibility of enhancing the commonly prescribed radiation therapy by simultaneous PDT.
Sandhya Clement, Wenjie Chen, Wei Deng, and Ewa Goldys, "Biodegradable nanoconstructs for targeted deep tumour therapy (Conference Presentation)," Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 104760C (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2289254.5751475988001.
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