Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells.

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of -15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC50 values reduced by 6.13-fold and 3.58-fold, respectively. PTX@zein-PEG/HA NPs induced the highest expression levels of apoptotic proteins, particularly PARP, in SKOV3 cells compared to PTX@zein-PEG NPs and free PTX. In summary, PTX@zein-PEG/HA NPs demonstrated potential as a delivery system for PTX in ovarian cancer.