Abstract:
Polyhistidine (PLH) was synthesized by ring-opening polymerization of anhydride, and then condensed with polylactide (PLA) to form an amphiphilic block copolymer (PLA-PLH). Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy (
1H-NMR) and dynamic light scattering (DLS) were used to characterize the structure and morphology of PLA-PLH nanoparticles. Using the anti-tumor drug 2-methoxyestradiol (2-ME) as a model drug, the drug delivery system PLA-PLH/2-ME was prepared by the solvent exchange method, and the drug loading and encapsulation efficiency were detected. At the cellular level, the inhibitory effects of the PLA-PLH/2-ME drug delivery system on CT26 colon cancer cells proliferation and migration were investigated. Finally, a fluorescent dye 1,1'-octacosyl-3,3,3',3'-tetramethylindocyanine iodide (DIR) was used as the fluorescent marker, and the distribution of PLA-PLH/DIR
in vivo was investigated. Results showed that PLA-PLH nanoparticles were successfully constructed, with an average particle diameter of (224.93±13.05) nm. When the mass ratio of PLA-PLH to 2-ME was 1∶0.6, the drug loading and encapsulation efficiency were (27.86±0.19)% and (64.38±0.50)%, respectively. In cellular experiments, PLA-PLH could significantly enhance the uptake of the drug system by CT26 cells. Compared with free 2-ME treated group, the cell proliferation inhibition rate and cell migration inhibition rate of CT26 cells treated with PLA-PLH/2-ME group were increased significantly.
In vivo imaging of mice and
ex vivo imaging of various major tissues studies showed that PLA-PLH nanoparticles could reduce the degradation of DIR in the gastrointestinal tract and enhance the accumulation of DIR in colon region after oral administration.