Oxygen‐Independent Supramolecular Nanoplatform for Photothermal‐Thermodynamic Therapy against Periodontal Anaerobic Infections

ABSTRACT

Radical‐based nanotherapeutics hold great promise for the treatment of periodontitis. However, the hypoxic/anaerobic microenvironment within periodontal pockets significantly restricts the antibacterial efficacy and clinical translatability of oxygen‐dependent radical therapy. By conjugating gold nanorods (AuNRs) with carboxylatopillar[5]arene (CP5), followed by the loading of 2,2'‐azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH) via host–guest recognition interactions, we develop an oxygen‐independent radical delivery nanoplatform (AIPH⊂CP5‐AuNR) to overcome the abovementioned barrier. Upon 808 nm near‐infrared (NIR) irradiation, AuNRs induce localized photothermal effects that not only disrupt bacterial biofilms via photothermal therapy (PTT) but also trigger the thermal decomposition of AIPH to generate oxygen‐independent alkyl radicals, thereby enabling thermodynamic therapy (TDT). Both in vitro and in vivo studies demonstrate that the cascaded PTT/TDT approach effectively eradicates pathogenic biofilms and alleviates periodontitis in rat models. This study not only proposes a novel oxygen‐independent therapeutic strategy but also expands the biomedical applications of supramolecular nanomaterials in stimuli‐responsive drug delivery.