Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO₂ for Synergistic Nucleus-Targeted NIR-II Photothermal and Hypoxia-Relieved Photodynamic Therapy.

Abstract

Bimetallic nanoparticles have received considerable attention owing to synergistic effect and their multifunctionality. Herein, new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO₂ nanoplates (H-MnO₂ ) are demonstrated for achieving not only nucleus-targeted NIR-II photothermal therapy (PTT), but also tumor microenvironment (TME) hypoxia relief enhanced photodynamic therapy (PDT). The Pd@Au nanoplates present a photothermal conversion efficiency (PTCE) as high as 56.9%, superior to those PTAs activated in the NIR-II region such as Cu₉ S₅ nanoparticles (37%), Cu₃ BiS₃ nanorods (40.7%), and Au/Cu_2-_x S nanocrystals (43.2%). They further functionalize with transactivator of transcription (TAT) moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO₂ (≈100 nm) loaded with photosensitizer Ce6 (TAT-Pd@Au/Ce6/PAH/H-MnO₂ ) to construct a hierarchical targeting nanoplatform. The as-made TAT-Pd@Au/Ce6/PAH/H-MnO₂ demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O₂ by reacting to endogenous H₂ O₂ to relieve the hypoxia for enhanced PDT, while the released small TAT-Pd@Au nanoplates can effectively enter into the nucleus to mediate PTT. As a result, a remarkable therapeutic effect is achieved owing to the synergistic PTT/PDT therapy. This hierarchical targeting, TME-responsive, cytoplasm hypoxia relief PDT, and nuclear NIR-II PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.