Construction And Properties Of Bismuth-based Persistent Luminescence Material Integrated Nanoprobes

Persistent Luminescence Nanoparticles（PLNP）are a class of photoluminescent materials with nanoparticles that absorb external excitation energy and continue to glow after excitation ceases.Near infrared（NIR）luminous PLNP can effectively avoid light scattering caused by in situ excitation,fluorescence interference of tissues and strong tissue penetration,and it is used in the research of integrative biological imaging and tumour diagnosis and treatment.Currently,the majority of PLNP reported are Cr³⁺as luminescent centers.However,the doping of heavy metal Cr³⁺has caused biosafety problems in long-term follow-up therapy.Therefore,they need to develop friendly Cr-free NIR luminescent PLNP is crucial.In this paper,we are mainly study the preparation,functionalization,theranostics of a novel Fe³⁺as the luminous center long wavelength emitting bismuth（Bi）based PLNP（Bi-PLNP）nanoprobe and it is application in tumour diagnosis,treatment and in vivo imaging.The main research contents and innovations are as follows:（1）Fe³⁺as the luminous center long-wavelength emission(Bi₂Ga_4-xO₉:x Fe³⁺(BGO:x Fe³⁺)x=0～1.8%)PLNP was prepared by co-precipitation method.The effects of Fe³⁺-doping amount,calcination temperature,calcination time,stirring temperature and p H value on the afterglow luminescence properties and crystal structure of BGO were investigated.The results show that the best composition of the prepared PLNP was Bi₂Ga_3.985O₉:1.5%Fe³⁺,the emission wavelength is 794 nm,the calcination temperature is900℃,the calcination time is 1 h,and the crystallization degree of BGO:x Fe³⁺PLNP is high.When stirred at room temperature and p H=7,the afterglow luminescence performance of the prepared materials is the best.The afterglow luminescence time can reach more than 3 h,and the average trapping energy depth is 0.7 e V.The mechanism of the afterglow luminescence of BGO:Fe³⁺PLNP is discussed.The prepared Bi-PLNP has excellent NIR afterglow luminescence and plays an important role in vivo imaging without background noise and deep tissue.（2）Firstly,hydroxyl group was formed on the surface of BGO:1.5%Fe³⁺PLNP（Bi-PLNP）,which is further modified as photothermal therapy（PTT）drug polydopamine（PDA）and photodynamic therapy（PDT）drug indocyanine green（ICG）,to construct a multifunctional optical/CT image-PTT/PDT combination therapeutic effect nanoparticle PLNP@PDA@ICG（labeled as PPI）.The photothermal/photodynamic properties of PPI were detected in vitro to evaluate the therapeutic potential of the composite probe.In addition,cell and physiological toxicity tests showed that A549 cells still had good survival rate and no obvious cytotoxicity at 200μg/m L of the probe.Meanwhile,14 days after injection of PPI probe,normal Balb/c male nude mice showed no significant tissue loss or pathological changes.In vivo imaging of Bi-PLNP showed that the probe has NIR long afterglow imaging capability in biological tissues.The CT imaging performance test shows that the probe has the capability of CT imaging and has great application value in cancer diagnosis.Finally,the study of PTT/PDT combination therapy for living tumours achieves the maximum therapeutic benefit.Therefore,this multifunctional nanoprobe can significantly improve the diagnosis and treatment of malignant tumours,which is of great significance in the medical field.（3）Fe³⁺,Eu³⁺co-doped long wavelength emitting Bi-PLNP(Bi_2-xGa_3.985O₉:1.5%Fe³⁺,x Eu³⁺x=0～2%)were prepared by co-precipitation method.The effects of Eu³⁺co-doping and calcination temperature on the afterglow luminescence properties and crystal structure of BGO:1.5%Fe³⁺PLNP were investigated.The results showed that the doping amount of Eu³⁺and the calcination temperature improved the afterglow luminescence properties of BGO:1.5%Fe³⁺PLNP.The best composition of the prepared PLNP was Bi_1.99Ga_3.985O₉:1.5%Fe³⁺,1%Eu³⁺,and the emission wavelength was at 798 nm.Eu³⁺co-doped BGO the afterglow luminescence time of BGO:1.5%Fe³⁺PLNP was extended from 3 h to over 8 h.In addition,the mean luminescence lifetime(τ_av)over the doping range of Eu³⁺increases from 13.77 s to 15.56 s.Hydroxyl group was formed on the surfaces of BGO:1.5%Fe³⁺,1%Eu³⁺PLNP,which was further modified as PTT drug PDA,PDT drug chlorin e6（Ce6）and chemotherapy drug doxorubicin（DOX）.A multifunctional nanocomposite probe for the synergistic therapeutic effect of optical/CT imaging-PTT/PDT and chemotherapy,PLNP@PDA@Ce6@DOX（labeled as PPCD）.The photothermal/photodynamic properties of PPCD were detected in vitro to evaluate the therapeutic potential of the composite probe.In addition,DOX simulation experiment results showed that,PPCD can achieve the drug loading and release function of DOX.