Rationally designed porous self-assembled nanoparticles for combinational chemo-photodynamic therapy

Despite notable advancements in cancer therapy, it remains a formidable global health challenge. The emergence of combinational treatments, particularly the integration of chemotherapy with photodynamic therapy (chemo-PDT), offers a glimmer of hope. This study introduces the development of zinc-coordinated quercetin-based self-assembled nanoparticles (ZnQ NPs) for advanced dual-mode cancer therapy. These cutting-edge ZnQ nanoparticles were synthesized in a rapid 15-minute single-step process, in stark contrast to the conventional hours or days required. Using Density Functional Theory (DFT) calculations, the optimal binding configurations of ZnQ NPs were precisely determined and further supported by band gap calculations between frontier molecular orbitals. Quercetin, a potent anticancer flavonoid, was used for the first time both as an active drug and as an organic ligand, resulting in pH-responsive nanoparticles with exceptional water dispersibility, stability, and biocompatibility. Additionally, these novel nanoparticles (NPs) were able to load chlorin e6 (Ce6), a photosensitizer known for its high singlet oxygen production, due to hydrophobic interactions within the pores. The ZnQ@Ce6 nanocomposite demonstrated remarkable Ce6 loading (19.03%) and significantly enhanced therapeutic effects, achieving a 77% cell inhibition rate under specific light conditions. This dual-functional platform, enhancing the solubility and bioavailability of Ce6 while harnessing the anticancer properties of quercetin, underscores the potential of ZnQ NPs in clinical nanomedicine, promising improved cancer treatment outcomes.