Preliminary Study On The Synergistic Treatment Of Tumors By Oxygen-supplementing Liposome Nanomedicine And The Process Of Liposome Transmembrane Penetratio

The complexity,diversity and heterogeneity of tumors make it difficult for a single treatment to completely cure cancer.Therefore,the development of multimodal collaborative treatment has become a research hotspot in cancer treatment.Among them,liposome nanocarriers have the advantages of high drug loading,synchronous delivery of hydrophilic and hydrophobic drugs,and improvement of pharmacokinetic parameters of drugs,which are widely used in combination therapy of tumors.In addition,cancer cell membrane-specific proteins enable nanomedicine to actively target homologous tumors and enhance the accumulation of drugs in tumor locations.At the same time,oxygen carrier perfluorohexane can increase the local oxygen concentration of tumors and enhance the therapeutic effect of tumors.Therefore,we used liposome and cell membrane to co-encapsulate near infrared photothermal agent Cy I,anticancer drug 10-hydroxycamptothecin and oxygen carrier perfluorohexane to prepare liposome nano drug particle size distribution,and the experimental results show that the introduction of perfluorohexane can significantly improve the oxygen loading of liposome,under the irradiation of near infrared laser,the nano drug can rapidly increase the temperature of perfluorohexane vaporization,thus breaking the structure of liposome and promoting the release of internal drug.In vitro cell experiments showed that the introduction of perfluorohexane and photothermal agents did not cause additional damage to cells,and the introduction of perfluorohexane could effectively enhance the intracellular photodynamic effect.At the same time,liposome nano-drugs can effectively kill cancer cells under the combined action of reactive oxygen species and 10-hydroxycamptothecin,and the membrane can actively target homologous tumor cells,resulting in more prominent therapeutic effect.The hemolytic toxicity of nanomedicines in the therapeutic concentration range is negligible and can be used for intravenous therapy.Subsequent animal experiments showed that due to the active targeting of homologous tumors by cell membrane,nano-drugs had obvious aggregation at the tumor site,and the tumor site in mice could reach the vaporization temperature of perfluorohexane after irradiation,which could effectively ensure the rapid release of drugs.In vivo experiments in mice showed that liposomal nanomedicine had excellent therapeutic effect on tumors.At the same time,organ tissue sections showed that no obvious organ damage was found in mice after two weeks of treatment,and the biocompatibility was good.The targeted oxygen-enriched liposome nano-drug synthesized in this paper provides a certain reference for the combined treatment of cancer and the improvement of the accumulation of nano-drugs in tumor locations.In addition,the study of the specific transport mode of liposome nano-drugs in tumor blood vessels is of great significance to improve the penetration ability of liposome blood vessels,improve the drug delivery efficiency of deep tumors and reduce the recurrence rate of tumors.The Pb S-Zn O mixture can undergo fluorescence resonance energy transfer,and the binding force between the two will be destroyed by solvent dilution of the mixture,and the fluorescence resonance energy transfer phenomenon will disappear,which provides technical support for the subsequent detection of liposome membrane penetration process using Lip(Pb S-Zn O).The results of subsequent experiments showed that the fluorescence of Zn O was effectively detected under long-term observation after the uptake of liposomes by cells.This experiment could effectively prove that Lip(Pb S-Zn O)based on fluorescence resonance energy transfer could be used for the detection of lipid structural integrity in biological environment,but the detection time needed to be too long to further improve the experimental conditions to obtain more accurate conclusions.This experiment provides a research idea and method for in-depth study of the endothelial-penetrating pathway and cell bypass pathway of nano-drugs,but further exploration and research are still needed to clarify how nano-drugs are delivered to tumor tissues.