Construction And Performace Study Of A Theranostic System Based On MnFe₂O₄ Composite Material

The diagnosis and treatment of malignant tumors and related diseases have always been a major challenge for humanity.In traditional medicine,contrast agents and therapeutic agents are often used to enhance the diagnostic and therapeutic effects on tumors.In recent years,the successful development of theranostic agents has combined imaging and therapeutic functions,effectively avoiding multiple injections of contrast agents and therapeutic agents,reducing toxic side effects,and improving the efficiency of diagnosis and treatment.However,due to the high heterogeneity of malignant tumors,previous single-mode imaging-guided single-mode treatment strategies are difficult to apply to all tumor patients,and their diagnostic and therapeutic effects struggle to meet clinical needs.Therefore,exploring advanced materials with multiple imaging modes and multiple treatment functions and optimizing their structures to enhance the diagnostic and therapeutic effects is the key to solving these problems.Mn Fe₂O₄nanoparticles are materials with high biocompatibility and strong magnetic resonance imaging capabilities.They have significant advantages in magnetic resonance imaging with high spatial resolution and good soft tissue imaging effects.However,their potential in multi-modal theranostic still needs further development.This paper focuses on the study of Mn Fe₂O₄nanoparticle clusters and constructs a series of theranostic systems,realizing magnetic resonance-photoacoustic imaging-guided multimodal therapy with accurate intra-tumor temperature monitoring.This paper presents a new approach for the design and construction of theranostic agents for tumors.The main research contents are as follows:（1）Mn Fe₂O₄ nanoparticle clusters were fabricated,their excellent photoacoustic imaging and photothermal therapy capabilities was demonstrated under excitation at 808 nm and 1064nm.This enabled magnetic resonance-photoacoustic imaging-guided photothermal therapy.Compared to Mn Fe₂O₄ nanoparticles,the relaxation rate of Mn Fe₂O₄ nanoparticle clusters increased by more than two-fold.Under the excitation of 808 nm or 1064 nm laser,Mn Fe₂O₄nanoparticle clusters show superior photoacoustic imaging performance,with the photothermal conversion efficiency increased by 2.4 times and 11.6 times,respectively.The 1064 nm laser exhibited a 13%higher transmittance in biological tissues compared to the 808 nm laser.Under the maximum permission exposure for the skin,1064 nm laser irradiation results in a 4.3-fold increase in the photothermal ablation efficacy of Mn Fe₂O₄ nanoparticle clusters towards tumor cells compared to 808 nm laser irradiation.（2）Mn Fe₂O₄ nanoparticle clusters were complexed with glucose oxidase,and achieving magnetic resonance-photoacoustic imaging-guided photothermal-starvation-chemodynamic multimodal therapy.Experimental results demonstrated that Mn Fe₂O₄-glucose oxidase generated reactive oxygen species in the tumor cell microenvironment,suppressing the expression of heat shock proteins in tumor cells,and alleviating the heat resistance of tumor cells.In comparison to Mn Fe₂O₄ nanoparticle clusters,Mn Fe₂O₄-glucose oxidase not only preserved its excellent magnetic resonance and imaging contrast capabilities,but also facilitated mild photothermal therapy（40-45℃）,thereby avoiding damage to surrounding normal tissues caused by conventional high-temperature photothermal therapy（above 50℃）and the resulting inflammatory reactions.This dual-mode imaging-guided multi-modal synergistic therapy achieves a killing efficiency exceeding 90%towards tumor cells,with a tumor suppression rate of 96.1%.（3）Na₃Hf F₇:Nd³⁺,Yb³⁺ratiometric near-infrared luminescent temperature sensing agents were developed.By combining it with Mn Fe₂O₄ nanoparticle clusters and glucose oxidase,magnetic resonance-photoacoustic imaging-guided photothermal-starvation-chemodynamic therapy with temperature monitoring inside the tumor was achieved.Its temperature sensitivity is 1.95%/℃,reaching an advanced level in the field.In vitro and in vivo experiments demonstrated that this composite material has excellent biocompatibility and high-sensitivity temperature monitoring capability inside the tumor,enabling mild photothermal therapy to be accurately and efficiently guided,and improving the safety of multi-modal synergistic therapy.