Cross-linked quaternized chitosan nanoparticles for effective delivery and controllable release of O. europaea phenolic extract targeting cancer therapy

Although current therapies for cancer patients have saved many lives, finding more effective remedies is still a challenge. To that end, we have begun to explore the potential of cross-linked quaternized chitosan nanoparticles (QCNPs) for synergistic improved therapeutic efficacy, effective delivery, and controllable release of O. europaea phenolic extract (OOPE), targeting liver and colon cancers. QCNPs showed a high percentage of OOPE loading content, encapsulation efficiency, and physicochemical stability, as evident by their high zeta potential. Additionally, QCNPs displayed pH-dependent OOPE release properties. In vitro studies demonstrated that the anticancer potentials of OOPE were significantly increased after encapsulation, with higher cytotoxicity towards HepG2 cells than Caco2 cells. A flow-cytometric study showed that OOPE-QCNPs increased the fraction of HepG2 cells in the sub-G1 phase and decreased the S phase proportion. In addition, OOPE-QCNPs can block DNA topoisomerase II beta. Interestingly, OOPE-QCNPs' ingredients damage liver cancer cells by raising the Bax/Bcl-2 ratio, a sign of intrinsic apoptosis. In conclusion, QCNPs may be an effective and safe option for the controllable delivery of natural bioactive extracts targeting long-term cancer therapy. Therefore, further research is warranted to investigate the efficacy and safety of these nanoplatforms for various cancer therapies.