Synthesis Of Novel Persistent Luminescence Nanoprobe And Its Biological Application

Cancer is one of the biggest premature killer.How to improve the efficiency of cancer diagnosis and treatment has become an important problem that needs to be solved urgently.Due to the advantages of high sensitivity,low ionizing radiation,simple and fast operation,fluorescence optical imaging has aroused intensive attention in the early diagnosis of tumors.As a novel fluorescence probe,persistent luminescence material（PLMs）can remain long-lasting luminescence after removal of the excitation light,which permits bioimaging with high sensitivity owing to the absence of background fluorescence interference from in situ excitation,and shows a broad application prospect in biomedicine.However,the excitation wavelength of current PLMs locates in the short-wavelength ultraviolet or visible band with shallow tissue penetration,making it difficult to re-excite efficiently in vivo,which seriously impedes the further application of the PLMs in biomedicine.Recently,the PLM activated by biological window have been developed,but its response efficiency in biological window still needs to be improved.Therefore,to further improve the re-excitation efficiency in vivo of PLMs,we prepared two kinds of PLMs,including the biological window activated Zn_1.3Ga_1.4Sn_0.3O₄:Cr³⁺,Y³⁺（ZGSCY）PLMs for efficient and repeatable imaging in vivo,and X-ray activated Zn₃Ga₂Ge₂O₁₀:Cr³⁺,Mn²⁺（ZGG:Cr,Mn）PLMs for bioimaging and photodynamic therapy（PDT）.The main contents are as follows:（1）We first prepared a new type of persistent luminescence material Zn_1.3Ga_1.4Sn_0.3O₄:Cr³⁺,Y³⁺excited by the light with a wavelength in the biological window（>650 nm）via high-temperature solid-state reaction.We systematically studied the influence of different co-doping concentrations of Y³⁺ions on the persistent luminescence properties,and compared them with traditional persistent luminescence materials such as Zn Ga₂O₄:Cr³⁺（ZGC）and Zn_1.3Ga_1.4Sn_0.3O₄:Cr³⁺（ZGSC）.The results show that the optical properties of persistent luminescence materials can be controlled by optimizing the concentration of Y³⁺ions and the persistent luminescence intensity of ZGSCY is approximately 163 times stronger than that of ZGC and about 2 times higher than that of ZGSC.The thermoluminescence spectra demonstrate that because of the addition of co-dopant Y³⁺,the trap concentration in the matrix increases,thereby improving the response efficiency of ZGSCY to the light with a wavelength in the biological window,and enhancing the persistent luminescence performance of ZGSCY.Additionally,we used the combustion method to prepare ZGSCY persistent luminescence nanoparticles（PLNPs）.After PEG modification on the surface of PLNPs,the PLNPs exhibit good biocompatibility and low toxicity.Moreover,in vivo imaging and passive tumor-targeted imaging can be achieved by irradiating with the LED after intravenous injection of PLNPs.The persistent luminescence material activated by biological window light addresses the problem of low re-activation efficiency in vivo and provides an effective idea for further biomedical application.（2）We prepared a novel Zn₃Ga₂Ge₂O₁₀:Cr³⁺,Mn²⁺persistent luminescence nanoparticles using X-ray as excitation source by combustion method and used for persistent luminescence imaging and photodynamic therapy.Under X-ray excitation,ZGG:Cr,Mn PLNPs have two emission peaks located at 532 nm and 698 nm,respectively.By adjusting the co-doping concentrations of Mn²⁺ions,both two emission peaks show excellent persistent luminescence performance and exhibit good repeatability.Based on the fluorescence resonance energy transfer between the green afterglow emission of ZGG:Cr,Mn and the photosensitizer rose bengal（RB）,we successfully constructed the RB-ZGG-FA PLNPs-mediated photodynamic therapy nanosystem by surface modification of RB and folate acid（FA）.Singlet oxygen（~1O₂）can be produced after X-ray excitation.Since the emission peak at 698 nm does not overlap with the absorption peak of RB,it can be used for persistent luminescence imaging.In vitro cell experiments proved that X-ray-excited RB-ZGG-FA processes tumor targeting ability and significant therapeutic effects in photodynamic therapy,indicating that it has broad application prospects in the diagnosis and treatment of tumors in vivo.