Preparation And Cancer Theranostic Validation Of Several Defective Inorganic Nanomaterials

Inorganic nanomaterials show great potential in the field of nanomedicine,and have been successfully applied in photothermal therapy(PTT),photodynamic therapy(PDT),sonodynamic therapy(SDT),chemodynamic therapy(CDT),etc.However,there are still some limitations of inorganic nanomaterials in the practical application of antitumor,such as low photothermal conversion efficiency(PCE),unsatisfactory effect of monomodal therapy,and low quantum yield of reactive oxygen species(ROS)greatly limit the application process of inorganic nanomaterials in clinical transformation.It’s worth noting,defective inorganic nanomaterials possess some special physical and chemical properties due to their unique electronic structure,such as special structure(varying coordination configurations),atomic property(variable valence state),atomic interaction(unsaturated bond),and electronic property(more active electron),etc.Therefore,this paper is devoted to the design and development of new defective inorganic nanomaterial system,micro-regulation of the properties of defective inorganic nanomaterials,coordination of multimode therapy,to improve its antitumor effect.Specific research contents are as follows:(1)Bi2Se3 nano-drug(VSe-BS)with rich selenium vacancy is prepared based on the co-modification of bovine serum albumin and folic acid for the second near-infrared(NIR-Ⅱ)light-triggered photothermal therapy.Initially,selenium vacancies on the crystal planes(0 1 5)and(0 1 11)of Vse-BS with similar formation energies can be distinctively observed via aberration-corrected scanning transmission electron microscopy images.The defect engineering endows VSe-BS with enhanced conductivity,making Vse-BS possess outstanding PCE(54.1%)in the NIR-Ⅱ biowindow.Tumor ablation studies indicate that Vse-BS possesses satisfactory therapeutic outcomes triggered by NIR-Ⅱ light.Meanwhile,this system shows good biocompatibility and metabolic properties and is a potential contrast agent for CT imaging and PA imaging.This study gives rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.(2)An amorphous IrTe2(G-IrTe2)with rich defects has been developed for the synergistic antitumor therapy of SDT,CDT,and mild PTT.G-IrTe2 as a sonosensitizer can produce ROS to achieve SDT under ultrasound(US)stimuli.The sonodynamic mechanism of G-IrTe2 is verified by theoretical calculation,that is the weak Ir-Te bond in G-IrTe2 was broken under US stimuli and free electrons were released,which combine with oxygen to form singlet oxygen(1O2),thus killing tumor cells.G-IrTe2 has catalase(CAT)-like and peroxidase(POD)-like activities.On the one hand,it can achieve self-supply of oxygen to enhance SDT effect.on the other hand,it can catalyze endogenous H2O2 to produce ROS to achieve CDT and achieve good tumor ablation effect.In addition,the ROS produced during treatment can cause mitochondrial dysfunction and down-regulate the expression of heat shock protein(HSP),thereby improving the efficiency of mild PTT.Therefore,G-IrTe2 has achieved excellent SDT/CDT/PTT synergistic antitumor therapeutic effect.This work provides a new research idea for expanding the application of inorganic amorphous nanomaterials in tumor therapy.(3)A unique Zn/Pt dual-site single-atom synergically augmented defective TiO2-based sonosensitizer is designed to overcome the key problem of rapid electron(e-)and hole(h+)recombination of traditional inorganic semiconductor sonosensitizer under US stimuli,which greatly limits the quantum yield of ROS.Initially,we explore the mechanism of SDT of Zn/Pt SATs through theoretical calculation and verify that the strongly coupled Zn atoms and Pt atoms have auxiliary effects on the excitation electrons of TiO2 under US at the atomic level,which effectively enhances SDT effect.Additionally,Zn/Pt SATs can produce sonoexcited holes and more ROS under US,which can enhance the ferroptosis of tumor cells.Therefore,the establishment of dual-site system represents an innovative strategy to enhance SDT and provides a typical example for the development of inorganic sonosensitizer in the field of antitumor.