pH-triggered prodrug micelles loaded with curcumin-terminated mono, di-pyrimidine as visual antitumor agents: study of simulated sustained release in gastrointestinal tract, fluorescence imaging, and bioactivity evaluation

This study designs and synthesizes two new curcumin–pyrimidine derivatives, which are encapsulated in four polymers, to obtain eight types of micelles. We tested the UV and fluorescence spectra of compounds P-1 and P-2 in different solvents and measured the UV and fluorescence spectra of 8 types of micelles in different pH environments. The release experiments of the simulated drugs in the gastrointestinal environment revealed that the release effects of PC-1 and PC-2 were greater for the 8 micelles. The encapsulation efficiency and drug loading of the PC-1 and PC-2 micelles were tested. TEM was conducted on PC-1 and PC-2, and the drug was evenly distributed on the carrier material, with PC-2 showing a regular spherical shape. The infrared spectra of polymer-C, P-1, P-2, PC-1, and PC-2 indicate that P-1 and P-2 are successfully encapsulated in the micelles. The AFM results indicate that PC-1 and PC-2 have an appropriate roughness, with PC-2 having a lower roughness than PC-1. The zeta-potential test results revealed its specific positive stability. Cell imaging experiments were conducted on PC-1 and PC-2 at different pH values, and the results revealed good biocompatibility. The calculation of Pearson's coefficient indicates that some complexes can enter the nucleus. HeLa cells, MGC cells, and L-02 cells were selected for cell proliferation experiments. The experimental results showed that the two micelles exhibited good biological activity on MGC and HeLa cells. Molecule docking was performed between P-1, P-2, and DYRK2, with binding energies of − 8.9 and − 9.7 kcal/mol, respectively, indicating that P-1 and P-2 have good binding ability with DYRK2.

Graphical abstract

The two new curcumin-pyrimidine derivatives were encapsulated in four polymers and studied through simulated sustained release in gastrointestinal tract, fluorescence imaging, and bioactivity evaluation.