Tumor Microenvironment Regulation Strategy For Tumor Therapy

Tumor microenvironment（TME）,including tumor cells and their microenvironment,is closely related to tumor formation and metastasis.In recent years,based on the biological characteristics of TME,such as hypoxia,acidity,overexpressed hydrogen peroxide and glutathione,a variety of treatments based on TME regulation strategies are still in the preliminary stage.Based on the TME,functional nanoparticles have been designed and prepared that are utilized to regulate the oxidation-reduction equilibrium of TME,further achieving efficient treatment of tumor.The main research contents are as follows:1.A strategy of tumor cell autophagy inhibition is used to enhance tumor starvation therapy.Tumor cells can protect themselves by autophagy.Therefore,inhibiting tumor cell autophagy is a key to improve the therapeutic effect to tumor.Based on this,we propose a strategy of tumor cell autophagy inhibition to enhance tumor starvation therapy.Hollow mesoporous organosilicon nanoparticles（HMON）co-loading glucose oxidase（GOx）and autophagy inhibitor-3-methyladenine（3-MA）are prepared to achieve an efficient tumor starvation therapy.Among them,GOx can consume O₂ in tumor area,and catalyze the glucose oxidation to produce gluconic acid and H₂O₂,which can significantly regulate the redox homeostasis of the tumor microenvironment.This not only achieves efficient tumor starvation therapy,but also inhibits the autophagy protection by autophagy inhibitor-3-methyladenine（3-MA）,to significantly enhance the effect of tumor starvation therapy.This research expands the application scope of tumor hunger therapy,and provides reference research idea for the development of other new tumor treatment technologies.2.The Fenton-like reaction,based on tiopronin copper nanoparticles,is used for tumor chemodynamic therapy.Chemodynamic therapy（CDT）,as a new cancer treatment technology,has abundant advantages.However,the limited H⁺and H₂O₂ concentration in the tumor microenvironment is a bottleneck problem that restricts the efficacy of CDT.Here,tiopronin copper are prepared to regulate the oxidation-reduction homeostasis of tumor,significantly improving the efficacy of tumor CDT,with a pH independent copper-based like-Fenton reaction.Tiopronin copper can react with the overexpressed GSH in the tumor area,resulting in Cu²⁺being reduced to be Cu⁺.This process is capable of efficiently catalyzing H₂O₂ in tumor to generate·OH with high oxidation activity.Moreover,it is worth mentioning that the copper-based Fenton-like catalytic reaction can be carried out in a neutral environment,which overcomes the acidic dependence of traditional iron-based Fenton reaction.Tiopronin copper can significantly change the oxidation-reduction homeostasis of the TME to inhibit tumor growth,indicating its great potential in the application of CDT in anti-tumor.This research further expands the application of tumor chemodynamic therapy,and provides a reference for other non-ferrous Fenton reaction anti-tumor therapy.