Cytotoxicity of non-viral gene vector polyamide amine dendrimers-hyaluronic acid polymer / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To study the cytotoxicity of polyamide amine dendrimers (PAMAM)-hyaluronic acid(HA)as a non-viral gene delivery vector in vitro. METHODS PAMAM-HA was synthesized by our laboratory. Cytotoxicities of various polymers on HeLa cells,Bel-7402 cells and HepG2 cells were evaluated by MTT assay. Apoptotic rates were determined by flow cytometry. RESULTS The cytotoxicity of PAMAM-HA polymer increased with the concentration of polymer(50-800 mg · L-1),the time of action(24-72 h), the number of generations of PAMAM(G4,G5) and decrease in the molecular mass(3850,17 200)and the graft density(5%-25%)of HA. After incubation with PAMAM G4-HA3850-5%or PAMAM G5-HA3850-5%for 24 h,the apoptotic rate of hepatoma cells—Bel-7402 cells was 4.5%and 9.9%,respectively. After incubation with complexes of PAMAM G4-HA3850-5%/DNA or PAMAM G5-HA3850-5%/DNA for 24 h,the viability of HeLa cells was more than 80%,which was lower than that of PAMAM G4/DNA和PAMAM G5/DNA. CONCLUSION Cytotoxicity of PAMAM modified by HA of different grafting density and quantity can be reduced ,suggesting the PAMAM is a promising non-viral gene vector.