The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1: 1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo.
[1]Pudong New Area Dist Zhoupu Hosp, Dept Gen Surg, Shanghai 201318, Peoples R China;
[2]Tongji Univ, Shanghai Tianyou Hosp, Dept Gen Surg, Shanghai 200000, Peoples R China;
[3]Fudan Univ, Shanghai Med Coll, Shanghai Canc Ctr, Dept Hepat Surg, Shanghai 200032, Peoples R China;
[4]Pujiang Community Hlth Serv Ctr, Dept Clin Med, Shanghai 201112, Peoples R China;
[5]Fudan Univ, Shanghai Peoples Hosp 5, Dept Gen Surg, Shanghai 200240, Peoples R China
(8.0+极速模式)