In Situ Growth of CuS/SiO₂-Based Multifunctional Nanotherapeutic Agents for Combined Photodynamic/Photothermal Cancer Therapy

A scalable and low-cost strategy is developed to fabricate a novel CuS/SiO₂-based nanotherapeutic agent for dual-model imaging-guided photothermal/photodynamic combined therapy. In this design, mesoporous silica nanoparticles (MSNs) with CuS bundled in the channel are obtained in aqueous solution via in situ growth route for the first time. Furthermore, to achieve a more efficient therapy, photosensitizer (complex Ir-2) and bovine serum albumin are sequentially assembled via layer-by-layer method. The as-prepared complex Ir-2 presents a remarkably high ¹O₂ generation (Φ_Δ = 1.3) under light illumination to offer effective photodynamic cell killing, and MSN/CuS exhibits high photothermal conversion efficiency (η = 31.7%) under illumination by 808 nm light to offer hyperthermia tumor ablation. In vitro and in vivo analyses show that the as-obtained nanotherapeutic agents exhibit excellent performance in tumor therapy even under irradiation with low power because of the high yield of ¹O₂ combined with the high photothermal conversion efficiency. Additionally, the nanotherapeutic agents are readily visualized in vivo via near-infrared fluorescence and thermal imaging. More importantly, based on the strategy of in situ growth and layer-by-layer assembly developed in this study, the development of other "all-in-one" multifunctional theranostic platform with high efficiency can be predictable.