Dual-targeted protein-coated PLGA nanoparticles for pancreatic cancer therapy: a novel approach using esculetin and curcumin.

The study aimed to investigate the effects of dual-targeted poly-lactic-co-glycolic acid (PLGA) nanoparticles (NP) containing esculetin (ESC) and curcumin (CURC), coated with membrane and cytosolic proteins, isolated from PID-PC (pancreatic islet-derived precursor cells) and MIA PaCa-2 cells, on pancreatic cancer. MIA PaCa-2 cells' viability treated with different combinations of the above-mentioned molecules and proteins was investigated in vitro. The sizes of all formed nanoparticles were determined by the "dynamic light scattering" method. The drug release profile of drug-containing PLGA-NP was examined. Cell death percentages and ROS levels were analyzed. Naked ESC showed an IC50 of 45.226 µg, while PLGA-coated ESC showed no measurable IC50. For CURC, no IC50 was observed in its naked form, but PLGA-CURC induced cell death starting at 6.25 µg. In the PLGA_ESC + CURC group, IC50 values were 75 µg for ESC and 9.375 µg for CURC. PLGA-coated PID-PC cytoplasmic proteins reduced ESC-treated cell viability by 46.42%, while the PLGA-coated MIA PaCa-2 cytoplasmic protein with ESC + CURC was most effective (41.11%). PLGA_ESC was released in 48 h, but protein coating accelerated release to 6 h. CURC showed delayed release, reaching only 30% at 72 h. PID-PC membrane proteins enhanced and prolonged release; MIA PaCa-2 cytoplasmic proteins suppressed it. Necrosis increased in all groups, while apoptosis and ROS decreased except in the CURC-treated groups. The novel membrane and cytosolic protein-coated PLGA-NP designed by our group, for the first time, has provided significant results in the treatment of pancreatic cancer.