| Because of its high incidence rate and high mortality,cancer has become one of the diseases that seriously threaten human health.In recent years,nano drugs have received attention in the field of tumor therapy.Although the delivery efficiency has significantly improved,the effect is still not ideal.Therefore,improving the delivery efficiency of drugs in tumors is currently an urgent problem to be solved.Obstruction of blood perfusion within a tumor is one of the main reasons for the low efficiency of drug delivery.The reason for this is the lack of lymphatic reflux at the tumor site,which leads to the retention of tumor interstitial fluid and its inability to flow back into the blood,resulting in an increase in interstitial hydraulic pressure at the tumor site,and a decrease in transvascular osmotic pressure difference that hinders the effective delivery of drugs into the tumor.Therefore,decomposing the water in the tumor interstitial fluid to reduce the pressure in the tumor interstitial fluid and promote drug delivery within the tumor is an effective solution.In addition,hunger treatment has received widespread attention in recent years,and intervention in glucose metabolism of tumor cells has become a research hotspot to improve the efficacy of hunger treatment.However,research has shown that other nutrients（such as lactic acid,amino acid,etc.）can also partially replace the role of glucose metabolism.Metabolically active tumor cells that grow deep in solid tumors can produce a large amount of lactic acid,causing lactic acid poisoning,and lactic acid can be re ingested by tumor cells to improve the metabolic rate,greatly affecting treatment efficiency.Therefore,it is necessary to design a nano platform that can effectively deliver to the depths of tumors and alleviate lactic acid poisoning by reducing tumor interstitial pressure（TIFP）.This study selected molybdenum disulfide（Mo S2）as a piezoelectric catalytic material,loaded with gold nanoparticles（Au NPs）and coated with tumor specific hyaluronic acid（HA）to construct a drug delivery system that can enhance intratumoral delivery and alleviate lactic acid poisoning.After MAH is aggregated to the tumor site through the EPR effect,HA on the drug surface can specifically target tumor cells,which can then be ingested by tumor cells.Au NPs can catalyze the reaction of glucose with O2to produce gluconic acid and H2O2,while Mo S2 has catalase like activity,which can react with H2O2 to produce O2 and·OH and consume glutathione（GSH）,thereby reducing the consumption of ROS,achieving high glucose consumption,while avoiding the constraints of hypoxia conditions,and enhancing the generation of ROS.In addition,under ultrasound stimulation,the piezoelectric catalytic performance of Mo S2 is triggered,which decomposes water in interstitial fluid,alleviates interstitial pressure,enhances drug delivery,achieves delivery of nano drugs to the depths of the tumor,fully consumes lactic acid inside the tumor,and responsively alleviates the phenomenon of lactic acid poisoning inside the tumor.The construction of the drug delivery system effectively enhances the deep penetration of drugs and alleviates lactic acid poisoning in tumors,providing an efficient method of hunger treatment. |
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