Bovine Serum Albumin-Templated Synthesis of Manganese-Doped Copper Selenide Nanoparticles for Boosting Targeted Delivery and Synergistic Photothermal and Photodynamic Therapy

Multifunctional nanohybrids integrating diagnostic imaging with photodynamic or photothermal therapy in a single agent feature the next generation of on-demand nanomedicine to meet the challenges in cancer therapy. In the present study, bovine serum albumin (BSA) protein through one pot biomimetic mineralization at its metal binding site synthesized and stabilized manganese-doped copper selenide nanoparticles (Mn:CuSe) with excellent biocompatibility, near-infrared absorption, water solubility, and rich functional groups for further bioconjugation. Mn doping not only imparted the magnetic resonance imaging (MRI) function to the Mn:CuSe@BSA but also enhanced its heat generation ability. By taking advantage of BSA's extraordinary ligand binding capacity, folic acid (FA) and chlorin e6 (Ce6) were then conjugated onto the BSA corona to construct the Mn:CuSe@BSA-FA-Ce6 nanohybrid for specific targeting of overexpressed folate receptor cancer cells. The obtained theranostic agent exhibited dual MRI signal enhancement and synergistic photothermal/photodynamic therapy (PTT/PDT) effect, which was demonstrated in vitro on HeLa cells. As a consequence, dual modal therapy with 1 min PDT laser irradiation doubled cell killing efficiency compared to the single PDT treatment. Having better efficacy regarding biocompatibility and synergistic light-activation therapy, the Mn:CuSe@BSA-FA-Ce6 nanohybrid holds the promise for image-guided cancer therapy.