Copper-hollow mesoporous polydopamine-polyacrylic acid nanoplatform enabling photoacoustic imaging-guided photothermal/chemodynamic therapy for osteosarcoma

Abstract

Osteosarcoma (OS) is an extremely destructive and lethal primary bone cancer, and its treatment remains a great challenge. Herein, a nanoplatform (HMPDA-Cu@PAA) was constructed by loading copper ions into hollow mesoporous polydopamine (HMPDA) and subsequently coating with polyacrylic acid (PAA), which exhibits dual responsiveness to the tumor microenvironment (TME) and exogenous 808 nm near-infrared (NIR) laser irradiation. The mutual conversion of Cu⁺ and Cu²⁺ in the TME endows HMPDA-Cu@PAA NPs with two enzyme-like activities: peroxidase-like (POD-like) and glutathione peroxidase-like (GPx-like) activities. HMPDA-Cu@PAA NPs exhibit a synergistic therapeutic capability that combines chemodynamic therapy (CDT), photothermal therapy (PTT), and the imaging capability of photoacoustic imaging (PAI). The as-prepared HMPDA-Cu@PAA stimulates the generation of toxic hydroxyl radicals (˙OH) in response to the specific TME and depletes intracellular glutathione (GSH) to kill MG63 cells with significant cytotoxic effect. Additionally, the localized temperature increase induced by PTT promotes the generation of toxic ˙OH, thereby achieving synergistic enhancement of PTT/CDT for OS therapy. As a robust nanozyme for PAI-guided multimodal treatment of OS, the HMPDA-Cu@PAA nanoplatform exhibits a remarkable tumor inhibition rate (TIR) of 81.36% in the MG63 tumor-bearing mouse models. Overall, this study presents a versatile and rationally designed nanoplatform, offering a promising paradigm for PAI-guided, TME-activated multimodal OS theranostics.