Construction And Biological Application Of NaErF₄ Multifunctional Nanoplatform

The traditional cancer treatment methods with surgical treatment,chemotherapy and radiotherapy as the main treatment,due to the disadvantages such as large side effects,prone to drug resistance and long treatment cycle,cannot guarantee the effect of tumor treatment,and seriously affect the patient's postoperative health recovery.Therefore,there is an urgent need for safer,more efficient,precise and controllable cancer treatment methods.Lanthanide-doped nanoparticles(LnNPs)can be excited by near-infrared laser and emits higher energy visible light or ultraviolet light.LnNPs have a large anti-Stokes shift,deep tissue penetration depth,no biological autofluorescence.Due to the abundant energy level structure,multi-band emission,flexible and tunable emission fluorescence and lifetime,LnNPs have also received extensive attention in biological imaging,detection and therapeutic applications.High energy transfer efficiency is the basis of LnNPs as energy donors for efficient biological detection and tumor treatment.However,the application and development of LnNPs are also affected by their lower energy transfer efficiency.Improving the energy transfer efficiency of LnNPs has important significance and research value for its application in biomedicine.In addition,fluorescence bioimaging and tumor treatment based on visible light and near-infrared areas are also affected by the scattering of biological tissues and biological autofluorescence,reducing imaging resolution and treatment efficiency.In addition,how to ingeniously modify LnNPs to give a single nanoparticle more functions and achieve an ideal tumor treatment effect has great research value in the field of nanomedicine.In order to realize the application of LnNPs in the field of biomedicine,this work has done research to reveal the energy transfer and energy migration mechanism of LnNPs and explored the multifunctional diagnosis and treatment application of new composite nanoparticles based on LnNPs in the field of tumor treatment.The main work of this paper is as follows:1.Design single Er³⁺nanostructures to study the relationship between energy transfer efficiency and energy transfer in nanosystems.The energy transfer efficiency of LnNPs as an energy donor is obtained by measuring the lifetime curve and theoretical calculations.It is found that the energy transfer efficiency is positively correlated with the doping concentration of Er³⁺.It is proved that increasing the concentration of Er³⁺can effectively improve the energy transfer efficiency of LnNPs,and a method for enhancing the energy transfer efficiency of LnNPs is proposed.Laid a theoretical foundation for promoting the application of energy transfer systems based on LnNPs.2.In order to achieve a safer multifunctional tumor treatment platform,the work in this section separates the imaging and treatment functions and controls the functions performed by the nanoplatform through excitation light to obtain more precise tumor treatment effects.Covalent coupling of Na Er F₄:0.5%Tm@Na YF₄@Na Yb F₄:0.5%Tm@Na YF₄@Na Gd F₄ and photosensitizer was used to construct 800/980 nm excitation light switching controlled imaging/photodynamic therapy nanoparticles.At the same time,the outer layer is coated with a calcium phosphate shell sensitive to the tumor microenvironment and loaded with doxorubicin and Mn²⁺to achieve drug release triggered by the tumor microenvironment.Meanwhile,both doxorubicin and photodynamic therapy can cause immunogenic cell death and inhibit the distant metastasis of tumor cells.More importantly,in addition to the NIR-? fluorescence imaging of LnNPs excited under 800 nm,Mn²⁺and Gd³⁺have paramagnetic properties.Therefore,MRI-T1 imaging can also be performed.The NIR-?fluorescence/MRI imaging-guided tumor microenvironment triggering chemotherapy/photodynamic therapy light switch nanoplatform is realized.This separation of imaging and treatment provides new ideas for safer tumor treatment.3.The complexity of the tumor microenvironment greatly weakens the effect of many treatment methods.In order to improve the treatment effect,we take advantage of the characteristics of increased temperature to promote the efficiency of chemical reactions and synergize the ferroptosis with photothermal treatment to achieve an efficient tumor treatment effect.Using LnNPs as a carrier to synthesize a porous black Bi₂Te₃ shell layer and load Fe₃O₄ particles,this tumor treatment nanoplatform has excellent photothermal conversion efficiency and has obvious photothermal therapy(PTT)effect under the excitation of near-infrared laser.Combined with the ferroptosis caused by Fe₃O₄ particles,tumor treatment can be performed at a lower temperature,avoiding side effects such as normal tissue damage caused by high temperatures.In addition,the process of tumor cell ablation can also cause the body's immune response,which also greatly reduces the risk of tumor recurrence and metastasis after the end of the treatment,and enhances the anti-tumor effect.At the same time,due to the stable luminescence properties of LnNPs,the strong attenuation of Bi₂Te₃ on X-ray and the strong absorption of the two at 800 nm wavelength,LnNPs@ Bi₂Te₃-Fe₃O₄ can perform fluorescence/X-ray/photoacoustic imaging to guide the process of tumor treatment.