Ferritin-nanocaged aggregation-induced emission nanoaggregates for integrated sensitive detection and treatment of gastric cancer

Gastric cancer remains a global health challenge due to late diagnosis and limited targeted therapies. Herein, we report a novel dual-targeted nanoplatform, AIE@HFn-scfv, integrating aggregation-induced emission luminogens (AIEgens) with human heavy-chain ferritin (HFn) conjugated to Claudin18.2-specific single-chain variable fragments (scFv). This nanoconstruct leverages HFn's natural affinity for transferrin receptor 1 (CD71) and scFv-mediated targeting of Claudin18.2 to achieve precise tumor localization. Bioinformatics analysis confirmed co-overexpression of CD71 and Claudin18.2 in gastric cancer tissues, validating their utility as dual targets. Physicochemical characterization revealed stable nanoparticles (∼17 nm) with pH-responsive fluorescence and efficient AIEgens encapsulation. <i>In vitro</i> studies demonstrated enhanced cellular uptake in Claudin18.2/CD71-positive MGC803 cells, achieving 52-fold specificity over normal cells. Multimodal imaging in subcutaneous and orthotopic gastric tumor models showed superior tumor-to-background ratios compared to single-target controls, enabling submillimeter tumor detection. Photothermal therapy induced tumor ablation at 53.6 °C, eradicating tumors in 80 % of treated mice without systemic toxicity. Biodistribution studies revealed reduced hepatic accumulation due to dual targeting, enhancing circulation time. This work establishes AIE@HFn-scfv as a promising theranostic platform combining sensitive detection, precise therapy, and biosafety, addressing critical unmet needs in gastric cancer management.