ABSTRACT
OBJECTIVE: To study the effect of different graft ratios of PEG on the toxicity in vitro and cellular uptake of PAMAM G5 dendrimers. METHODS: Nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy were used to confirm the structure of PEG-PAMAM G5 dendrimers with four different graft ratios. The particle size and Zeta potential of the nanoparticles were determined by nanoparticle size-Zeta potential analyzer. The toxicity in vitro,cellular uptake, and intracellular localization were tested by hemolysis assay,cytotoxicity assay,cellular uptake test,and laser scanning confocal microscope images,respectively. RESULTS: The particle sizes of dendrimers with PEG graft ratios of 7.8%,14.1%, 20.3%,and 24.2% were (17.05 ± 1.77), (20.77 ± 1.02),(21.68 ± 1.04),and (23.19 ± 0.54) nm,respectively. The Zeta potential decreased from (25.57 ± 1.37) mV of PAMAM G5 to (9.27 ± 0.40) mV of PEG31-PAMAM G5. In addition, the hemolytic toxicity and cytotoxicity of PAMAM G5 dendrimers also markedly decreased especially at high concentrations because of PEG modification. Moreover, the PEG-PAMAM G5 dendrimers with particle diameter of nearly 20 nm not only could be taken in by HBMEC cells, but also accumulated in the cell nucleus. CONCLUSION: Modification of PEG can greatly reduce the toxicity of PAMAM G5 dendrimers in vitro, and the higher the degree of modification, the more obvious is the attenuated effect. The PEG-PAMAM G5 dendrimers with particle diameter larger than 20 nm still can be taken in by HBMEC cells and accumulate in the cell nucleus, which provide a foundation for the further research using modified PEG-PAMAM G5 as a basic carrier for genes and nuclear targeting agents in nano medicine.