Low Molecular Gelatin Coated Multifunctional Cationic Lipid Nanoparticles Inhibit Tumor Growth And Metastasis

Breast cancer is the leading cause of cancer-related mortality and threating women's life and health.Metastasis is one of the major reasons for treatment failure of breast cancer in clinical therapy.Nanotechnology has a good application prospect in inhibiting the growth and metastasis of malignant tumor.In this paper,a low molecular gelatin coated multifunctional cationic lipid nanoparticle was prepared via modified emulsion evaporation method.The potential to inhibit tumor growth and metastasis of the multifunctional nanoparticles was preliminarily evaluated.The optimized nanoparticles showed a uniform size of(112.8?6.2)nm with a narrow size distribution and zeta potential of(-3.27?0.15)mV.TEM results showed that GNP exhibited a compact and spherical morphology without adhesion.The drug encapsulation efficiency and drug loading of three encapsuled drugs were 89.54±5.16%?98.95±8.22%?60.13±6.42% and 1.62±0.36%?0.83±0.11%?1.06±0.32% for DTX,Quercetin and Imatinib,respectively.In the in vitro release assay,GNP exhibited a sustained release behavior in PBS(pH 7.4)and a significant enzyme sensitivity.To evaluate the in vitro features of GNP in cell level,the cellular uptake,cytotoxicity,cell apoptosis,cell scratches and Western Blotting assay were carried out against 4T1 cells.GNP exhibited the most cytotoxicity among the experimental groups and promoted the apoptosis of 4T1 cells remarkably.The CLSM and flow cytometer results demonstrated that GNP nanoparticles could significantly enhance cellular uptake.The cell scratches assay and Western Blotting assay showed that GNP could inhibit the expression of MMP-9 and reduce the ability of 4T1 cell movement.Based on the construction of the 4T1-bearing model mice,the ability to inhibit tumor growth and metastasis were estimated in vivo.The results demonstrated that GNP could remarkably suppress tumor growth and metastasis.As a result,the novel gelatin-coated multifunctional nanoparticles prepared in this paper could be a very useful approach to suppress breast cancer growth and metastasis.