Design,Preparation And Performance Of Metal Non-oxide Nanoparticles For Novel Tumor Gaseous Microenvironment Regulation Therapy

Tumor microenvironment（TME）is an eternal subject in research on nanotheranostics and nanomedicine.In recent years,the related work of tumor imaging and treatment has gradually moved from responding and monitoring to regulating and changing of TME.The Tumor Microenvironment Regulation Therapy has become a novel idea with great prospect for clinical application.Tumor gas microenvironment（TGME）,known as an essential part of TME,plays an indispensable role in tumor proliferation,metastasis,invasion and drug resistance.In this thesis,2 kinds of inorganic metal non-oxide nanoparticles,with high activity in acidic tumor tissue,have been successfully synthesized,and show considerable potential in TGME regulation therapy of cancers,which are summarized as follows:（1）Artificial Anaerobic Creating and Dormancy Inducing via Acidic-responding TPZ Coated Mg₂Si for Tumor Gaseous Microenvironment Regulation TherapyAn improved self-propagation high-temperature synthesis（SHS）method was developed to synthesize the Mg₂Si nanoparticles.After washed and modified with TPZ and PVP,the functional constructed TPZ-MNPs with acid-activity,oxygen-depletion and hypoxia-sensitizing designments was obtained.TPZ-MNPs show the great potential and considerable performance to efficiently reduce oxygen concentration,induce cell dormancy and eventually cause cell apoptosis.The in vitro and in vivo experimental results showed that oxygen depletion and hypoxia-induced radical act synergistically to kill tumor cells,implying that TPZ-MNPs shows potential as an evocating agent of cell-dormancy gaseous microenvironment regulation therapy.（2）Acidic-responding Hydrogen Selenide Releasing MnSe₂ for Gas-assisted Photothermal TherapyTraditional solvothermal synthesis method was chosen to to fabricate MnSe₂nanoparticles with high dispersity and stability.When modified with PVP,a nano agent MSPs was obtained to specifically release hydrogen selenide in tumor tissue,decrease the expression of GPx4 and GR protein and raise the thermosensitivity of tumor cells,and meanwhile protects surrounding normal tissue from rapid heating radiction.The in vitro experimental results showed that,compared with laser alone,Gas-assisted Photothermal Therapy could kill tumor cells efficiently.