Synergistic Therapy For Tumor Microenvironment Specificity

At present,the treatment of tumors has become an important problem that should be solved in the world.However,the current treatment systems for treating tumors generally have the following limitations-poor targeting.Therefore,the ideal tumor treatment system should be able to destroy tumor cells in large quantities without harming normal cells.In this paper,five tumor synergistic treatment systems were designed and constructed for the difference between tumor-specific microenvironment?pH⁵.4,high concentration glutathione,hypoxia and thermal instability?and normal cells.The specific design is as follows:1.The chapter prepared a photothermal/medication treatment system?Au@MnO₂@PDA/5-FU?under the dual response of gold-based acid and glutathione by normal temperature synthesis.Under the short-term stimulation of near-infrared light,Au and polydopamine?PDA?exhibited photothermal conversion ability.The final cytotoxicity and imaging experiments demonstrated the biocompatibility of the system and had inhibitory effect on tumor cells?Hela cells?.2.The chapter?MB@SiO₂@PDA/5-FU?was synthesized by low-temperature synthesis.Under the stimulation of near-infrared light,the nanoparticles could be degraded by the organism after blood circulation,and PDA would also exhibit thermal phenomenon.The final tumor cell imaging also showed that the system was at a concentration of 50?g/mL,which could achieve dual treatment effect obviously and also prevent normal tissues from harm.3.Mesoporous silica prepared by alkali etching was used as carrier of5-FU@m-SiO₂@PDA/GOD nano-system.PDA was used as photothermal reagent,glucose oxidase?GOD?as nutrient depleting agent and 5-fluorouracil?5-FU?as a drug model to form a triple synergistic treatment.In the drug sustained-release experiment,the system had a response to the tumor microenvironment,and the killing power of the system on tumor cells was verified in MTT and tumor imaging characterization.4.The chapter was based on the organic metal framework?MOF?nanomaterial UIO-66-NH₂ as the drug carrier of the system,and the drug model 5-FU was loaded in the carrier to form the final 5-FU@UIO-66-NH₂@PDA nanometer system.The MOF carrier was degradable in a slightly acidic environment to induce controlled release of the drug,and the thermal energy was generated by the photothermal reagent PDA under the trigger of NIR light,Finally,the inhibition of the tumor cells and the protective effect on normal cells were demonstrated in the toxicity test and the flow cytometry test.5.The chapter adopted hydrothermal method and layer coating method to combine Mn²⁺doped upconversion nanomaterials(UCNPs(Mn²⁺))with MOF carrier UIO-66-NH₂ to form nanosystem UCNPs(Mn²⁺)/UIO-66-NH₂/MB/MnO₂@PDA.PDA,MB was as a thermal reagent and photosensitizer,respectively,as a biocatalyst,MnO₂ in this system catalyzed the production of O₂ by H₂O₂ in tumor cells,the maximum emission wavelength of UCNPs(Mn²⁺)partially overlapped with the maximum absorption of MB under NIR light irradiation.Leading to the energy resonance effect,the O₂ was sensitized by the photosensitizer to active oxygen to inhibit the growth of the tumor.And the MTT toxicity and tumor imaging experiments proved that the system had inhibition on tumor growth.