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

## TL;DR

A new nanoplatform combines detection and treatment of gastric cancer by targeting two proteins, improving diagnosis and therapy precision.

## Contribution

A dual-targeted theranostic nanoplatform integrating AIEgens and ferritin for sensitive detection and photothermal therapy of gastric cancer.

## Key findings

- The AIE@HFn-scfv nanoplatform achieved 52-fold specificity in targeting gastric cancer cells compared to normal cells.
- Multimodal imaging enabled submillimeter tumor detection with superior tumor-to-background ratios in mouse models.
- Photothermal therapy using the platform eradicated tumors in 80% of treated mice without systemic toxicity.

## Abstract

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. In vitro 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.

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