Near-infrared Luminescence Nano Afterglow Materials For Bioimaging And Tumor Therapy

The study of integrated multifunctional nano-platform for diagnosis and treatment is always attracted people’s attention.The near-infrared（NIR）luminescent persistent material has the unique luminescent property that can store energy after being excited by the light source and keep emitting NIR luminescent signals for a long time after the excitation is stopped.Due to the advantages of sustainable imaging without background fluorescence of this material,the application of this material in the biomedical field gradually attracts people’s interest,especially as an in vivo imaging tool.There are some important research contents,like how to effectively enhance the penetration of imaging luminescence signals of NIR afterglow materials,avoid the interference of background fluorescence of biological tissues,improve the signal-to-noise ratio of images,and target treatment of tumors without harming normal cells,as well as in-depth application research,have to be studied to expand the biological application of this material.To solve these problems,the synthesis of nano-sized NIR luminescent long afterglow materials to composite with other materials to form the multi-functional nano-platform is the design idea of realizing the nano platform of the integrated platform for diagnosis and treatment.In this paper,the size and luminescence properties of NIR luminescent persistent materials are improved by using different synthetic methods and ion co-doping,and then the prepared nanoparticles were used to combine with other materials to achieve the purpose of integrating bioimaging and tumor therapy.There are three works have been designed and completed as follows:1)Nano-size NIR luminescent persistent material,m Si O₂@Zn_1.1Ga_1.9O₄:Cr³⁺（SZGO）,was designed and synthesized by using nano mesoporous silica（m Si O₂）as the template.And then the multifunctional nanoparticle m Si O₂@Zn_1.1Ga_1.9O₄:Cr³⁺@HKUST-1（HSZGO）was obtained by further coating HKUST-1.This nanoplatform showed NIR-I afterglow luminescence signal in mice for more than 30 min and was targeted-activated by H₂O₂ and H₂S which are overexpressed in tumor cells.The tumor of H22 tumor-bearing mice can be cured through the synergistic effect of chemodynamic therapy（CDT）and photothermal therapy（PTT）without harming other normal tissue cells.This multifunctional platform can be used for biological imaging and tumor treatment,which combines NIR-I luminescent persistent material with functional MOF material,and provides a research idea with a reference value for the design of the integrated imaging and treatment platform.2)In the second work,we further applied the m Si O₂ and extended the multifunctional luminescence application of NIR-I long persistent material.Firstly,Au nanoparticles（Au NPs）were used as the photothermal agents to load on the mesoporous and surface of m Si O₂,and then the multimodal luminescence afterglow nanoparticles,with up-conversion luminescence and NIR persistent luminescence,were formed by loading Zn Ga₂O₄ which co-doped with Cr³⁺,Yb³⁺,and Er³⁺on the m Si O₂@Au nanoparticles to obtained the multifunctional nanoparticles m Si O₂@Au@Zn Ga₂O₄:Cr³⁺,Yb³⁺,Er³⁺（SAZ）.And finally,the photosensitizer zinc phthalocyanine（Zn Pc）was loaded to synthesize the composite nanoparticles,m Si O₂@Au@Zn Ga₂O₄:Cr³⁺,Yb³⁺,Er³⁺@Zn Pc（SAZZ）,which can be used for biological imaging and tumor treatment.SAZZ nanoparticles showed an obvious photothermal effect under 980 nm laser irradiation,and the up-conversion luminescence and NIR afterglow luminescence can activate Zn Pc to generate singlet oxygen（¹O₂）for tumor photodynamic therapy（PDT）.SAZZ nanoparticles can be accumulated at the tumor site,and used for tumor-targeted imaging under the excitation of 645 nm.Under the illumination of 980 nm,it can inhibit the growth of tumor cells through the synergistic therapeutic effect of PTT and PDT.It has great application and research potential in the field of biological diagnosis and treatment.3)To improve the tumor targeting effect of the nanoplatform and remove the size restriction of the template,in this work,we used ZIF-8 which is sensitive to slightly acidic environment,to encapsulate the small-sized（<10 nm）multimodal luminescent nano-size afterglow material Zn_2.9Na_0.2Ga₄Ge O₁₁:Cr³⁺,Yb³⁺,Er³⁺（ZGGO）,the photothermal reagent Au NPs and the photosensitizer Zn Pc,to obtain the multi-functional tumor targeting nanoplatform ZGGO/Au/Zn Pc@ZIF-8（ZAZZ）.The ZIF-8outer layer of ZAZZ nanoparticles is decomposed under the special acid environment of tumor cells,and the encapsulated ZGGO,Au NPs,and Zn Pc were slowly released,then,penetrated through the cell membrane and absorbed by tumor cells after.After entering tumor cells,ZGGO nanoparticles emitted up-conversion luminescence and NIR-I afterglow luminescence that can generate ¹O₂ for photodynamic therapy through energy transfer with Zn Pc under 980 nm excitation.Au NPs exhibited excellent photothermal properties under a 980nm laser as photothermal treatment.This photothermal treatment can effectively enhance the effect of photodynamic treatment to achieve the goal of synergistic treatment.At the same time,the targeted tumor imaging ability of ZAZZ in mice can be observed under the excitation of 645 nm.Therefore,the multifunctional nanoparticles ZAZZ can target tumors NIR-I imaging,PTT&PDT synergistic therapy in vivo.