Study Of Multifunctional Nanoprobes Based On Tumor Hypoxia Microenvironment

Hypoxia is one of the most common features in solid tumors as lung cancer,which causes a complex environment,such as composition changes of gene transcription and expression to proteins and content promotion of hydrogen peroxide,resulting in invasion,metastasis,damage or death of malignant tumor cells.In addition,hypoxia could also lead to drug resistance of tumors,accelerate deterioration.Thus,exploring a targeted stratagem to treat hypoxia can effectively inhibit the proliferation,invasion and metastasis of clinical tumors.In view of this,we developed a multifunctional nanoprobe,PLGA-BSA-MnO₂-IR780 nanoparticles,using MnO₂ as matrix material,modified with fetal bovine serum protein?BSA?,combined with photothermal therapy by adding photosensitizer IR780,with PLGA as carrier material for treatment of hypoxic tumors.In this study,we utilize high-efficiency response of MnO₂ with hydrogen peroxide?H₂O₂?in acidic environment to generate oxygen?O₂?,improving the internal hypoxic state while consuming H⁺,alleviating the micro-acid environment,and generating Mn²⁺with high T1 magnetic resonance relaxation.The results show that the prepared nanoparticles can enhance magnetic resonance imaging on the tumor site after respond with endogenous H₂O₂ in A549,promote the expression of reactive oxygen species?ROS?in tumor cells under normoxia,and effectively inhibit tumor growth after combined with photothermal therapy.In addition,we established different hypoxic models to simulate the microenvironment of tumors in vitro,explore the quantitative relationship between oxygen concentration and tumor treatment effects.Dynamic balance mechanism of the hypoxia microenvironment was verified with the changes of intracellular ROS content after co-incubated with the prepared nanoparticles at different oxygen concentrations.The results show that tumor growth was inhibited to the greatest extent under moderate hypoxia?5%oxygen concentration?after treatment with the developed PLGA-BSA-MnO₂-IR780 nanoparticles.During study,we found a quantitative relationship between tumor treatment efficacy and oxygen concentration,which can accelerate the progress of tumor treatment to a certain extent,provide a theoretical basis for tumor treatment under hypoxic microenvironment.The research verified that hypoxia is related to oxygenation in tumors,different biological reactions varies with oxygen concentration,anoxia time and its own energy demands.Further quantitative study of therapeutic efficacy with oxygen concentration is of great significance for clinical treatment,effectively promotes dynamic balance of intracellular inducing factors,regulates drug resistance,accelerates apoptosis,inhibits tumor growth.