Nepenthes-inspired saliva-amassing low-dosed risk-factor alerted detecting (SALAD) mouthguard for forewarning of the intraoral cancer

Oral cancers pose a significant challenge to global public health with devastating incidence and poor prognosis, highlighting the urgent need for early detection and intervention. Herein, inspired by the unique water-collecting structure (peristome) of the Nepenthes pitcher plant, an innovative saliva-amassing low-dosed risk-factor alerted detecting (SALAD) system was integrated into the wearable mouthguard for in situ, specific, and sensitive detection of tumor necrosis factor-alpha (TNF-α) in saliva, serving as a potential early indicator for oral cancers. This system employed an efficient liquid amassing (LA) module to collect and immobilize intraoral biomarkers in dynamic and complex saliva environments. Moreover, the Aggregation-Induced Emission (AIE)-related fluorescent signal was activated directly in the center of the mouthguard in conjunction with a household UV lamp, simplifying the detection process and amplifying the visibility of the diagnostic readings. Encouragingly, the SALAD mouthguard demonstrated exceptional capability in detecting target biomarkers in simulated intraoral environments. Promisingly, it received highly positive support from the volunteers who underwent preliminary testing with the SALAD mouthguard. Overall, validated by numerous simulated and realistic in vitro and in vivo tests, the SALAD mouthguard was demonstrated to act as a promising candidate for forewarning of oral cancer, highlighting potential for clinical translation and improving patient care experiences.