| Because of its strong affinity with iron,iron chelator was the first to be used in the treatment of iron overload diseases in the body.Current studies have found that the proliferation and differentiation of tumor cells are usually accompanied by the disorder of iron metabolism and the activation of related cell pathways catalyzed by iron.Therefore,the use of iron chelating agents can inhibit the expression of related signaling pathways,so as to play a certain anti-tumor effect.Deferasirox(DFX),as the first oral iron chelator approved by the US FDA,was the first to be used in the treatment of iron overload caused by anemia.Current research shows that DFX has certain effects on certain malignant tumors.The anti-tumor activity of DFX is affected by factors of low bioavailability and insufficient targeting.Objective: In order to improve the bioavailability of DFX,the albumin nano drug delivery system is used to encapsulate DFX.Through BAC cross-linking and cRGD modification,the bioavailability of DFX is improved and the nanoparticles are given certain targeting and responsive release capabilities.Method: The method of detecting DFX was established by high performance liquid chromatograpy,and the method of single factor investigation was used to optimize the BSA concentration,p H value,volume ratio of water to ethanol,and mass ratio of DFX to BSA during the preparation of albumin nanoparticles;Perform related characterization studies on the prepared albumin nanoparticles for particle size,polydispersity coefficient(PDI),and Zeta potential,and use high-performance liquid chromatograpy methods to determine the encapsulation efficiency and drug loading;use the method of gel electrophoresis,to verify the synthesized cRGD-BSA.The stability of albumin nanoparticles was studied in different media;the in vitro release of nanoparticle drugs was studied by simulating the environment of normal tissues and tumor tissues.Through the MTT cytotoxicity test,the inhibitory effect of free deferasirox(DFX)and albumin nanoparticles on tumor cells in 24 hours was explored;the cell viability/dead staining test was performed on the free deferasirox(DFX)and albumin cells treated with nanoparticles were subjected to qualitative analysis of cell apoptosis;FITC was used to label nanoparticles,and the uptake of nanoparticles by cells was studied by fluorescence microscopy and flow cytometry;The anti-tumor activity of DFX and albumin nanoparticles in vivo was studied.Results: DFX has a good linear relationship in the concentration test,and the precision test also meets the detection standards.After synthesis,the size of albumin nanoparticles is below 220.0nm,the PDI value is less than 0.2,the particles are negatively charged,and the nanoparticles are spherical as a whole Type,uniform size and good dispersion.The result of gel electrophoresis proved the successful synthesis of cRGD-BSA.At the same time,the nanoparticles can show good stability in both water and 10% serum solution.At the same time,albumin nanoparticles are beneficial to the release of DFX in a tumor environment with a high concentration of GSH and achieve the purpose of controlled release of drugs.Cellular MTT toxicity test and cell live/dead staining test show that cRGD-BSA-DFX-NPs albumin nanoparticles have the strongest tumor inhibitory effect;cRGD-modified nanoparticles have stronger cell uptake and tumor targeting.ability.The in vivo anti-tumor results showed that cRGDBSA-DFX-NPs albumin nanoparticles had the strongest inhibitory effect on tumor growth compared with other groups.Conclusion: By using albumin nanoparticles as a drug delivery carrier to carry DFX,the bioavailability of DFX is improved,the side effects are reduced,and the antitumor effect of DFX is enhanced.The internal cross-linking of albumin nanoparticles by BAC gives the nanoparticles the ability to respond to the release of the tumor environment,and the modification of cRGD gives the nanoparticles the ability to target tumors. |
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