A Novel Supramolecule Combining the Pharmacological Benefits of Berberin and Catechin for the Prevention and Treatment of Cervical Cancer

Natural small molecule catechins (CC) show significant promise in preventing and treating cervical cancer due to their remarkable anti-HPV, antioxidant, and anti-tumor properties. However, the poor stability, fragile chemical structure, and high hydrophilicity of CC seriously affect the ultimate anti-tumor effect of the drug. In order to overcome these drawbacks of CC, berberine (BBR) assisted CC assembly with the same anti-cervical cancer effect was selected, taking advantage of the easy alkaloid self-assembly properties of polyphenolic compounds. We report a novel dual component (BBR and CC) directed self-assembly mode. The two small molecules were assembled into highly drug-loaded, homogeneous supramolecules (341 nm) by π-π stacking at 60℃, pH 7.4, the reaction time of 1 h, and the molar ratio of BBR to CC of 2:1. The supramolecular self-assembled nanoparticles (NPS) not only exhibit excellent stability, high assembly rate (86.42%), and sustained release performance, but also have stronger cell binding and uptake capabilities. In addition, the assembled supramolecules (BBR-CC NPS) retain the excellent biological characteristics of BBR and CC. It had good anti-inflammatory and antioxidant effects. More importantly, this NPS can disrupt mitochondrial membrane potential, increase reactive oxygen species (ROS) release, and induce apoptosis in cancer cells. These results indicated that BBR-CC NPS can serve as a carrier-free drug delivery system that enhances drug stability while exhibiting synergistic pharmacological activity. This provides more possibilities for the application of natural small molecules in cancer treatment and drug delivery. Additionally, it also presents new insights into the integration mechanism of traditional Chinese medicine.