Application Of Near-infrared Responsive Copper Matrix Composites In Chemodynamic Therapy

Tumor Microenvironment(Tumor Microenvironment TME)is the internal environment for tumor cells generation,growth and metastasis,including not only tumor cells themselves,but also surrounding cells,capillaries,and biomolecules.Compared with the internal environment of normal tissues,significant differences in the tumor microenvironment are manifested in hypoxia,acidity,hydrogen peroxide(H₂O₂)and glutathione(GSH)overexpression,and chronic inflammation.In recent years,chemodynamic therapy based on the biological characteristics of TME has emerged.However,the treatment mode has the problem of low Fenton reaction rate in tumor cells during the procedure,which obviously reduces the treatment effect.Therefore,three types of functionalized copper-based nanocomposites based on the weak acidity and reducing properties have been designed and synthesized for regulating the oxidation-reduction equilibrium steady state of the tumor microenvironment,effectively inhibiting tumor growth though enhanced chemodynamic therapy.The specific research contents are as follows:(1)Based on the fact that photothermal can promote Fenton and Fenton-like reactions to move forward,we have prepared nanocomposites(Cu₂O-MoS₂)with good biocompatibility and excellent photothermal properties by electrostatic adsorption of Cu₂O by molybdenum sulfide(MoS₂)sheet.Under the irradiation of NIR-I 808 nm laser,Cu₂O-MoS₂ nanoparticles produce hyperheat in the tumor microenvironment,and Mo⁴⁺ions on the surface of MoS₂ accelerate the conversion of Cu²⁺ions to Cu⁺ions,which further improves the efficiency of Fenton-like reaction.Cell results showed that cytotoxic substances(·OH)produced by nanoparticles could disrupt homeostasis and induce cell apoptosis in combination with photothermal therapy,showing excellent photothermal enhanced CDT efficacy.(2)In this work,Phase change material(PCM)coated Cu S nanoparticles and ultra-small Ca O₂ nanoparticles to prepare thermally responsive nanoparticles with self-supply of H₂O₂(Cu S/Ca O₂@PCM).By near NIR-I(808 nm)laser irradiation,the photothermal effect produced by Cu S will melt PCM and rapidly release Cu S and Ca O₂,and further trigger Ca O₂ to produce a large amount of H₂O₂ and Ca²⁺in the tumor microenvironment.The Fenton-like reaction between self-supplied H₂O₂and Cu S produces·OH with strong oxidation activity,which causes oxidative stress and death of tumor cells.Meanwhile the thermal energy generated by Cu S enhances the efficiency of Fenton-like reaction.(3)PEG modified Cu₂MoS₄nanomaterials were synthesized by a simple one-step hydrothermal method.Due to the catalase catalytic activity of the polyvalent Cu⁺/²⁺Mo⁴⁺/⁶⁺contained in Cu₂MoS₄,Fenton-Like reactions can occur in the tumor microenvironment.Nanoparticles exhibit excellent photothermal properties and produce reactive oxygen species(ROS)under the light response of NIR-II region(1064 nm).Under the irradiation of 1064 nm laser,Cu₂MoS₄ aqueous solution shows excellent photothermal effect,photothermal conversion effect reaches 42%,which can significantly improve the Fenton-Like reaction rate.In addition,the NIR-II has a deeper tissue penetration depth,so the material can be used for photodynamic and photothermal therapy of 1064 nm photoresponse.