Preparation Of Molybdenum Diselenide Composite Nanodrugs And Anti-Cervical Cancer Properties

Cancer has become the primary disease that threatens human health.Although researchers have developed many new treatment strategies,the treatment effect is still not satisfactory.The root of the problem lies in the low efficiency of drug delivery in vivo.The heterogeneity of tumor microenvironment is a key obstacle for the penetration of nano-drugs into the tumor.The disorganized blood vessels and uneven blood flow distribution in the tumor area,coupled with the leakage caused by immature neovascularization and poor lymphatic drainage,lead to a large amount of tissue fluid retention in the tissue stroma,which makes the interstitial fluid pressure much higher than the vascular venous pressure.The drug is mainly driven by convection to transport from the blood vessel to the stroma,so the reverse pressure difference affects drug delivery.In order to improve the efficiency of drug delivery,inspired by nano-catalytic medicine,the in vivo catalytic reaction was initiated under specific external stimulation to transform non-toxic drugs into toxic components in situ.The specific damage to tumor cells can be achieved through the high selectivity and specificity of the reaction,and the harm to normal tissue can be avoided.In this study,the piezoelectric material MoSe₂ was selected as the basic drug,and the piezoelectric catalytic performance was optimized by laser accelerated electron-hole separation and Schottky barrier formed between metal and semiconductors to hinder the recombination of charge.In this way,on the one hand,through catalytic hydrolysis,reduces interstitial hydraulic pressure,promotes drug delivery;on the other hand,the production of a large amount of ROS under ultrasound and light stimulation will cause oxidative stress,and combining with light and heat to damage tumor cells.Firstly,MoSe₂ nanoparticles were synthesized by hydrothermal method,and then Pt was in situ reduced to MoSe₂ nanoparticles by photodeposition to form MoSe₂/Pt nanoparticles,whose surface was modified with polyethyleneimine,and then loaded with photosensitizer indocyaninegreen by electrostatic adsorption.Finally,the tumor homologous cell membrane was wrapped on the surface of nanoparticles to form a MoSe₂/Pt-ICG@M biomimetic nano-drug system.Under the modification of homologous cell membrane,MoSe₂/Pt-ICG@M nanoparticles can escape the phagocytosis of tumor immune system.Through the form of receptor-ligand binding,the nanoparticles are endowed with homology recognition and homing properties by adhesion molecules expressed on homologous tumor cell membrane,and accurately target to the tumor region.Under ultrasonic vibration,the interior of MoSe₂ was polarized and deformed to form a built-in electric field.As a powerful driving force,piezoelectric potential promoted acousto-generated charge transfer and made electron hole separation.At the same time,the excitation of light would accelerate this process,and the existence of Schottky barrier at the interface between MoSe₂ and Pt hindered the recombination of electron holes,which enhanced the performance of piezoelectric catalytic hydrolysis.The water in the interstitial liquid would be decomposed by redox catalytic reaction and converted into oxygen,hydrogen and hydroxyl radicals.This not only relieves the hypoxic tumor microenvironment,reduces the expression of hypoxia-inducible factor,reduces the tumor multidrug resistance,but also reduces the water content in the tissue fluid,thus reduces the interstitial hydraulic pressure,promotes the blood perfusion of the tumor site,which enables more nano-drug MoSe₂/Pt-ICG@M to penetrate into the deep layer of the tumor.Hydrogen and ROS produced during this period can damage mitochondria and reduce the production of ATP.In addition,with 808 nm laser irradiation,the drug causes a surge in local temperature of the tumor and kills tumor cells by thermal ablation.At the same time,ICG can also further enhance oxidative stress to kill tumor cells.This design shows excellent therapeutic effects in vivo and in vitro,and provides a new idea for the combination of drug delivery efficiency and tumor therapy through catalytic reaction.