Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin

Breast cancer remains a significant global health challenge, emphasizing the pressing need for innovative therapeutic approaches. Our thorough research investigates the potential of mesoporous polydopamine nanoparticles (MPDA) as a targeted treatment for breast cancer. Meticulously crafted, these nanoparticles were loaded with honokiol (HK), which is a natural product, and then coated with functionalized hyaluronic acid (HA) to boost their ability to target breast cancer cells that overexpress CD44 receptors. The deep penetrating and photothermal (PTT) composite nanosystem combined with low-dose metformin (Met) improves the efficacy of synergetic therapy against breast tumors. The designed nanosystem exhibited exceptional biocompatibility and stability, suggesting its suitability for therapeutic use. Our <i>in vitro</i> studies demonstrated that the nanosystem precisely targeted and penetrated breast cancer cells, resulting in significant cell death. Additionally, <i>in vivo</i> studies showed that the nanosystem markedly inhibited tumor growth compared to the control group. This tumor-inhibiting effect was due to the combined action of the encapsulated HK, free Met, and the photothermal effect induced by near-infrared laser irradiation. This combination potently stimulates the expression of cleaved caspase-3 and cleaved PARP proteins, ultimately triggering cell apoptosis and effectively curbing tumor proliferation. Our research not only underscores the promising potential of nanoparticles for targeted breast cancer therapy but also sets the stage for further exploration and development of novel nanomedicine-based therapeutic strategies.