Fabrication Of Persistent Luminescence Gel For High-efficient Photodynamic Therapy

Objective:Bioavailable persistent luminescence material can be used as an ideal internal light source for long-term photodynamic therapy?PDT?,which can solve the problems caused by external sources such as ionizing radiation damage,long-term radiation-induced tissue ablation and insufficient self-illumination efficiency.But persistent luminescence material inevitably suffers from low utilization efficiency,weak persistent luminescence?PL?due to corrosion and screening processes.Therefore,we show a facile and smart“turning solid into gel”strategy to fabricate persistent luminescence hydrogel for high-efficient persistent luminescence-sensitized PDT.Subjects and Methods:Preparation of persistent luminescence material?PLM?and persistent luminescence hydrogel?PLH?:PLM was synthesized by a hydrothermal method in combination with sintering in air.Then PLM and alginate were mixed in an aqueous solution,and the mixture was magnetically stirred to make them sufficiently uniformly mixed.Then the CaCl₂ solution was dropwise added to form PLH.The PLH's hardness,viscosity was tuned by varying the accounts of Ca²⁺and persistent luminescence material.Characterization and application of persistent luminescence hydrogel:The prepared PLM and PLH were characterized.The cytotoxicity and vivo toxicity of the persistent luminescence hydrogel were comprehensively evaluated through cellular MTT assay,histopathological analysis of Kunming mice in metabolic process and weight monitoring of Kunming mice.The amount of singlet oxygen produced in vitro was obtained by measuring the absorbance of DPBF.The accumulation ability of PLM in tumors was evaluated through a small animal fluorescence imaging system.The effects of photodynamic therapy in vitro and in vivo were respectively assessed by cellular MTT assays and tumor size monitoring.Result:The prepared PLH exhibited strong and long-lasting luminescence,100%utilization efficiency of PLM and good injectability,which can be easily injected into the tumor site in mice without leaking through the injection channel.The intelligent introduction of PLM with a big size into tumors via hydrogel injection facilitates the accumulation of PLM in tumors and minimizes the side effects induced by the penetration into bloodstream and other tissues of PLM.MTT assay,histopathological analysis in metabolism process and weight monitoring of Kunming mice showed that the persistent luminescence nanoparticles and hydrogel were little toxic.High-efficient PDT in vitro and in vivo were achieved using the hydrogel as an internal light source.Conclusion:In this work,we show a facile and smart“turning solid into gel”strategy to fabricate persistent luminescence hydrogel?PLH?for high-efficient persistent luminescence-sensitized PDT.The PLH with intact persistent luminescence of PLM and red light renewability as a robust internal light source permits superior repeated persistent luminescence sensitized PDT of tumors.The proposed PLH provides a promising way to take full advantages of the persistent luminescence for PDT,possessing 100%utilization efficiency of PLM,intact persistent luminescence,and facile synthesis and administration processes.More importantly,the“transforming solid to hydrogel”strategy shows great potential in the utilization of diverse theranostic agents regardless of their hydrophilic and hydrophobic features.