Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO 2 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 MnO 2 nanoplates (H‐MnO 2 ) 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 Cu 9 S 5 nanoparticles (37%), Cu 3 BiS 3 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 MnO 2 (≈100 nm) loaded with photosensitizer Ce6 (TAT‐Pd@Au/Ce6/PAH/H‐MnO 2 ) to construct a hierarchical targeting nanoplatform. The as‐made TAT‐Pd@Au/Ce6/PAH/H‐MnO 2 demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O 2 by reacting to endogenous H 2 O 2 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.