Study On Lactoferrin-modified Gambogic Acid Liposomes For The Colorectal Cancer Treatment

Colorectal cancer is a relatively common type of cancer of the digestive system and one of the diseases that threaten human life and health.The disease is related to the economy development.With the development of economy,the incidence and mortality of colorectal cancer in China are increasing year by year.There are many factors that induce colorectal cancer,including: poor eating habits,exposure to the microbial environment,inflammatory immune response,gene mutations.The treatment of colorectal cancer includes surgery,radiotherapy,chemotherapy,immunotherapy,and so on.Although chemotherapy has a certain curative effect,it will also produce greater side effects.Gambogic acid has a significant therapeutic effect on colorectal cancer,mainly by inducing tumor cell autophagy,apoptosis,inhibiting tumor angiogenesis,inducing tumor cells to produce excessive reactive oxygen species(ROS)and other mechanisms to inhibit tumor growth.Because gambogic acid is a poorly water-soluble drug,it is difficult to apply by injection.Targeted formulations can improve the solubility of poorly soluble drugs,and can target the delivery of drugs to tumor sites,and are suitable for the delivery of poorly soluble drugs.Research purpose: This study intends to construct lactoferrin-modified liposomes,encapsulate the insoluble drug gambogic acid,and use lactoferrin to mediate targeted drug delivery to colorectal cancer cells to promote the production of large amounts of reactive oxygen species by tumor cells(ROS),induces tumor cell apoptosis and autophagy,and achieve the purpose of treating colorectal cancer.Research method: The gambogic acid-loaded liposomes were prepared by the thinfilm dispersion method,and lactoferrin was modified on the surface of the liposomes to form lactoferrin-modified liposomes.The particle size and potential of liposomes were measured by a Malvern particle size analyzer,and the appearance of liposomes was observed by a cryo-electron microscope.High performance liquid chromatography was used to determine the drug loading and drug encapsulation efficiency of liposomes,and the SDS-PAEG gel electrophoresis experiment was used to detect the modified content of lactoferrin.The stability of liposomes was investigated in serum-containing PBS buffer solution.Flow cytometry and fluorescence microscopy are used to detect cell uptake,and flow cytometry,Western Blot,and q PCR experiments are used to detect the anti-tumor mechanism of the drug and its effect on tumor-associated macrophages.Research result:1.Prepared liposome targeting preparations containing gambogic acid(lactoferrin modified liposomes),with an average particle size of about 110 nm,PDI less than 0.2,good stability,regular morphology,encapsulation efficiency,The drug loading can meet the needs of the experiment.2.Cell experiments show that lactoferrin-modified liposomes have high cell uptake efficiency,can induce the production of ROS,promote the apoptosis and autophagy of colorectal tumor cells,and can also inhibit the formation of vascular endothelial cells.3.Animal experiments show that lactoferrin-modified liposomes have good antitumor effects and low toxic and side effects.Research conclusion: This project has designed a tumor-targeting lactoferrinmodified liposome loaded with gambogic acid.The targeted preparation has good stability,and the encapsulation efficiency and drug loading can meet the requirements.This preparation has a good curative effect on colorectal tumors,and its tumorinhibiting effect is mainly related to mechanisms such as promoting ROS production,inducing cell apoptosis and autophagy,and inhibiting angiogenesis.