Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo.
Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival.
Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China ; Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China.
Mingrong
M
Cheng
Xiaoyan
X
Gao
Yong
Y
Wang
Houxiang
H
Chen
Bing
B
He
Yingchun
Y
Li
Jiang
J
Han
Zhiping
Z
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D004337:Drug Carriers; D005472:Fluorouracil
5-fluorouracil; chemotherapy; liver cancer; targeted therapy