Since Von Tappeiner [1] first proposed photodynamic reaction, phototherapy has attracted extensive attention from scientists. Photodynamic therapy (PDT), as a new treatment for tumor and many diseases, has the advantages of non-invasive, low toxicity, repeatable treatment and high selectivity. Photodynamic therapy is the interaction of photosensitizers, light and molecular oxygen, which depends on the accumulation of photosensitizers in tumor cells. Photosensitizers transfer photon or electron energy to surrounding oxygen under light irradiation, thus generating various forms of reactive oxygen species, which directly trigger the internal apoptosis pathway related to mitochondrial oxidative damage [2]. Normal cells have already metabolized the photosensitizer, so they are not affected by the treatment.
Fig.1 Schematic representation of PDT mechanism [3]
Photosensitizer, as the core factor of photodynamic therapy, affects the therapeutic effect to a great extent, and light, as an important factor, also plays an important role. Therefore, PDT research focuses on the development of more active photosensitizers and enhanced light penetration.
In order to make the therapeutic effect more ideal, scientists are committed to the synthesis of intelligent photosensitizer with optimized performance. From the initial small molecular organic photosensitizers, such as porphyrin derivatives, phthalocyanine, indole, BODIPY to two-photon excitation technology, then to organic skeleton compounds, and finally to the present nano-photosensitizers [4], the performance of photosensitizers and photodynamic therapy effect has been greatly optimized.
Fig.2 Schematic illustration of PS-loaded NPs for localized photodynamic destruction of pancreatic cancer (PCa)
The effect of conventional photodynamic therapy is limited by the influence of light penetration. In order to effectively solve this problem, Geoffrey D. Wang [5] developed a new derivative of PDT, X-PDT, based on Chen's idea [6] that X-ray overcame the shallow penetration effect of photodynamic therapy. It was proved that X-PDT can effectively kill Radioresistant non-small cell lung cancer cells(H1299). Enhanced effects were also observed in vitro and subcutaneous tumor models or in vivo with percutaneous lung transplantation of H1299 cells.
Fig.3 In vivo therapy studies
(a) Representative bioluminescence images of mice treated by X-PDT, RT, MC540-SAO: Eu@mSiO2 and PBS on Day 1, 7, and 12. MC540-SAO: Eu@mSiO2 nanoparticles were intrathoracically injected to the mice. In the RT and X-PDT groups, a single dose X-ray radiation of 5 Gy was applied to the tumor area, with the rest of the body covered by lead. (b) Tumor growth, measured by monitoring BLI signal changes at different time points. (c) Ex vivo bioluminescence images taken immediately after tissue dissection. The organs were organized in the following order: top row (from left to right): intestine, spleen, liver and skin; bottom row (from left to right): muscle; brain; lung; heart and kidneys. (d) BLI signals from the lungs. Based on ROI analyses on (c). (e) Representative photographs of lungs taken from the X-PDT and control Groups. (f) H&E staining with tumor tissues from different treatment groups. Scale bars, 100 µm [5].
References
- Raizada, K.; et al, Photodynamic Therapy, StatPearls Publishing: Treasure Island, FL, USA, 2020.
- S.W. Tait.; et al, Mitochondria and cell death: outer membrane permeabilization and beyond, Nat. Rev. Mol. Cell Biol. 2010,11, 621–632.
- Niculescu, Adelina.; et al, Photodynamic therapy—an up-to-date, Review. Applied Sciences, 2021, 11, 3626.
- Minhuan Lan.; et al, Photosensitizers for Photodynamic Therapy, Adv. Healthcare Mater. 2019, 1900132.
- Geoffrey D. Wang.; et al, X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy, Theranostics, 2016; 6(13): 2295-2305.
- Chen W.; et al, Using nanoparticles to enable simultaneous radiation and photodynamic therapies for cancer treatment. Journal of nanoscience and nanotechnology. 2006; 6: 1159-66.
