ABSTRACT
Objective To prepare and evaluate As2O3 loaded polyethylene glycol-polycaprolactone-polyethyleneimine (PEG-PCL- PEI, PPP) nanoparticles (As2O3-PPP-NPs) in vitro. Methods As2O3-PPP-NPs was prepared by one-step electrostatic loading method using PPP triblock polymer as carrier. The drug loading and entrapment efficiency of the nano-drug were determined by ICP-OES. In vitro drug release property was studied by the dialysis bag method. Hemolytic toxicity of As2O3-PPP-NPs was investigated by UV spectrophotometry. Cytotoxicity of As2O3-PPP-NPs on human cervical cancer (HeLa) and human hepatocellular carcinoma cells (HepG2) was evaluated by MTT assay. Finally, ICP-OES and confocal microscopy was used to investigate the uptake efficiency and uptake mechanism of As2O3-PPP-NPs by HepG2 cells. Results The prepared nano-formulations were spherical and well-dispersed with particle size of 88.7 nm. The encapsulation efficiency and the drug loading rate were (92.75 ± 3.83)% and (4.39 ± 0.26) %, respectively. In vitro release studies showed that As2O3-PPP-NPs had the characteristics of sustained release and low pH responsive drug release, which could achieve specific drug release in the tumor environment. The loading of As2O3 neutralized the positive charge of PPP, and the hemolytic toxicity of the material was reduced. MTT assay showed that the median lethal concentrations (IC50 values) of As2O3-PPP- NPs to HeLa and HepG2 cells were 6.24 μmol/L and 5.85 μmol/L, respectively, which showed strong inhibiting effect on tumor cells. Cellular uptake studies showed that As2O3-PPP-NPs was rapidly taken up by cells due to positively charged surface and featured the lysosomal escaping ability, so the drug could be released in the cytoplasm and exert its anti-tumor effect. Conclusion As2O3-PPP-NPs exhibits significantly sustained and low pH responsive release characteristics, and has the ability to escape from lysosomes. As2O3-PPP-NPs is a potential drug delivery system against solid tumor.