[Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5-fluorouracil loaded polylactic acid nanoparticles].

OBJECTIVE: To explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice. METHODS: Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed. RESULTS: The tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05). CONCLUSION: Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.

[Preparation of 5-fluorouracil encapsulated in amphiphilic polysaccharide nano-micelles and its killing effect on hepatocarcinoma cell line HepG2].

BACKGROUND & OBJECTIVE: Biodegradable colloidal nano-micelles is a novel targeting drug delivery and controlled release system, which could prolong the biological half-life and lighten the toxicity of chemotherapeutant, meanwhile, present fine biocompatibility. This study was to prepare the biodegradable 5-fluorouracil (5-FU)/DEX-g-PLA nano-micelles, and investigate their killing effect on hepatocarcinoma cell line HepG2 in vitro and in vivo. METHODS: 5-FU/DEX-g-PLA nano-micelles were prepared by 'self-assembly'. Its morphology was observed by transmission electron microscopy. The encapsulating efficiency of 5-FU was determined by ultraviolet spectrophotometry. The in vivo releasing of 5-FU from nano-micelles was investigated by high-performance liquid chromatography (HPLC). The inhibitory effect of 5-FU/DEX-g-PLA on HepG2 cells in vitro was measured by MTT assay. RESULTS: 5-FU/DEX-g-PLA nano-micelles were round or elliptical; the diameter was about 50 nm. The encapsulating efficiency was about 9.3%. The concentration of 5-FU released from 5-FU/DEX-g-PLA nano-micelles was sustained for longer time than that of the naked drug. The in vitro inhibition rate of cell growth was similar in 5-FU/DEX-g-PLA group and naked 5-FU group (58.8% vs. 58.0%, P>0.05); the in vivo inhibition rate of tumor growth was significantly higher in 5-FU/DEX-g-PLA group than in naked 5-FU group (73.1% vs. 57.5%, P<0.05). CONCLUSION: 5-FU/DEX-g-PLA nano-micelles can effectively inhibit the growth of HepG2 cells.