Study Of Photodynamic Therapy Based On Bioluminescence Resonance Energy Transfer

Photodynamic therapy is a new way for tumor therapy,because PDT has many advantages,such as well targeted ability,low level of pain for patients,thus,the PDT is widely accepted by many countries.However,conventional photodynamic therapy is severely constrained by the limited light-penetration depth in tissue.In recent years,many researchers tried to develop new ways to increase the penetration depth in tissue,for example,tried to use near-infrared light,Cherenkov rays and X-rays to increase the depth of the light source,but these methods still remained limited-penetration of biological tissue.In addition,there are other disadvantages caused by external light source,such as skin photosensitivity and photothermal injury are also common concerns from the patients receiving PDT treatment.In this study,we applied a kind of endogenous bioluminescence in the study of photodynamic therapy to replace the external light source,thus eliminating the defect of tissue penetration depth.In the experiment,we chose biodegradable polymer PLA and PLGA,and the photosensitizer Rose Bengal(RB)which is typical photosensitizer that can generate singlet oxygen with a high quantum yield to prepare nanoparticles as “drug” by reprecipitation method.Spectroscopic characterizations indicated that there was an obvious spectral overlap between the absorption of RB molecules and the bioluminescence emission spectrum,which allowed for the occurrence of BRET,and the photosensitizer RB could be effectively activated and generate ROS species for killing cancer cells and the inhibition of tumor growth.We respectively studied the efficiency of therapy both in vivo and in vitro,cytotoxicity experiment verified that single materials do not have toxicity to the cells,however the photosensitizer nanoparticles under the effect of bioluminescence resonance energy transfer showed good cell toxicity,which verified the in vitro effect of treatment.The in vivo experiment was based on the H22 tumor-bearing mice,and the result showed that the bioluminescent resonance energy transfer effect of photodynamic therapy(BRET-PDT)can well inhibit tumor growth.In addition,the fluorescence images showed that BRET-PDT method caused more than 50% cancer cells death compared to the control groups.In vivo bioluminescence imaging indicated that photosensitizer nanoparticles have high stability under bioluminescence system in vivo environment and the fluorescence is available to be observed.In conclusion,the results above showed that that PDT based on bioluminescence resonance energy transfer(BRET-PDT)method can effectively kill cancer cells and significantly inhibit tumor growth in the absence of external light irradiation.The BRET-mediated phototherapy provides a promising approach to overcome the light-penetration limitation in photodynamic treatment of deep seated tumors.