| Hepatocellular carcinoma(HCC)is a primary cancer and the third most common fatal cancer.Although in the early stages,HCC does not cause disease and has no obvious clinical symptoms,if left untreated,the survival rate of patients with hepatocellular carcinoma will be very low when it progresses to an advanced stage.HCC can be treated by some methods such as liver transplantation,surgical resection and local ablation.Unfortunately,however,hepatocellular carcinoma is recurrent and metastatic,and therefore only some patients with HCC are eligible for treatment.Transcatheter hepatic artery embolization(TACE)is widely used in the treatment of hepatocellular carcinoma.TACE involves transporting an embolic agent through a microcatheter to the blood vessels in the body to block them.It is one of the most important basic techniques of interventional radiology treatment because of its minimally invasive nature,full image guidance and accurate localization,high reproducibility and efficacy,and has become a research hotspot for the treatment of advanced liver cancer.Natural degradable microspheres can be safely transported in vivo and act as embolic agents for embolization therapy to improve the clinical outcomes of liver cancer treatment due to their excellent drug encapsulation ability,biocompatibility,swelling,hemocompatibility,and porous imaging function,which is a boon to patients.Therefore,this study utilizes modified gelatin(Gel MA),magnetic nanoparticles(MNPs)and lipid-soluble drugs as materials,and after ultrasonic dispersion,the multifunctional embolic hydrogel microspheres are prepared by the principle of photocrosslinking and microfluidic technology,and the excellent performance of the hydrogel microspheres is verified by characterizing various physicochemical properties of the microspheres and in vitro biological experiments,and the optimal preparation scheme is selected.Details are as follows:(1)This study provides a method and application of multifunctional embolic microspheres containing magnetic nanoparticles and drug coupling,in which methacryloylated gelatin(double bond modified),magnetic nanoparticles and glycogenic adriamycin were mixed and ultrasonically broken to prepare embolic microspheres using microfluidic technology.The formed microspheres have a diameter size between 100-400 μm and a stable particle size,showing a porous shape with good drug loading(12% drug loading),and excellent swelling and degradation properties allow the microspheres to act as embolic agents,and the hydrogel microspheres were initially verified to be implantable and can be safely transported in vivo.GM@MNPs@GD microspheres also have superparamagnetic properties and can be used as magnetic resonance imaging(The microspheres are not toxic to normal cells(NIH 3T3),but have a significant killing effect on human hepatocellular carcinoma cells(Hep G2).(2)In this experiment,we continued to develop a multifunctional embolic microsphere with magnetic nanoparticles coupled with an anti neovascular drug.Methacrylate-based gelatin,magnetic nanoparticles and sorafenib drug were mixed as substrates to prepare GM@MNPs@SF multifunctional embolic microspheres by the principle of photocrosslinking.The hydrogel microspheres were also distributed between 100-400 μm in diameter and evaluated by SEM,swelling and degradation experiments,blood and various cell experiments,which showed that the hydrogel microspheres had a rough and porous surface,uniform particle size,good swelling and degradation properties,and good physicochemical properties and blood compatibility(the hemolysis rate was below 5%).In vitro cellular experiments demonstrated that the hydrogel microspheres were not toxic to mouse fibroblasts(NIH 3T3),but could inhibit the growth of human umbilical vein endothelial cells(HUVEC)and human hepatocellular carcinoma cells(Hep G2),and the microspheres could also inhibit the formation of neovascularization and further inhibit tumor growth.In summary,two multifunctional embolic hydrogel microspheres were designed and evaluated in this study,both of which exhibited good physicochemical properties and hemocompatibility.The hydrogel microspheres were not toxic to normal cells,while the drugloaded microspheres could both kill hepatocellular carcinoma cells and inhibit the formation of neovascularization.These results established that embolic microspheres can be used as embolic agents for the treatment of hepatocellular carcinoma and have broad application prospects. |
