[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).


CONCLUSIONS
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.
Huang
Kai-hong
KH
Institute of Gastroenterology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Liu
Jian-hua
JH
Wang
Lin-yun
LY
Zhu
Zhao-hua
ZH
Chen
Qi-kui
QK
Min
Jun
J
Chen
Ru-fu
RF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009389:Neovascularization, Pathologic; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; C033616:poly(lactide); D005472:Fluorouracil