Theranostic biofluorescent nanocomposite for fluorescence-guided delivery of cinobufagin and apoptosis modulation in gastric carcinoma

Gastric carcinoma (GC) is a highly aggressive gastrointestinal cancer with a poor prognosis, largely due to chemotherapy resistance and the complexity of the tumor microenvironment. Cinobufagin (CB), a bioactive compound derived from toad extract, has demonstrated promising anti-tumor activity but suffers from poor solubility and systemic toxicity, limiting its clinical application. To address these challenges, a multifunctional biofluorescent nanoplatform, iron-responsive fluorescent compound I (I-DASA), 3-aminopropyltrimethoxysilane (APTMS), and coordination polymer 1 (CP1) co-assembled system (I-DASA-APTMS@CP1@CB), was designed and synthesized via a one-pot strategy for simultaneous CB delivery and tumor cell detection. In this system, I-DASA provides a rapid and selective fluorescence response, APTMS enhances structural stability and surface functionality, and CP1 facilitates efficient drug loading and controlled release. Fluorescence sensing results revealed a strong and rapid response toward AGS gastric cancer cells with a detection limit of 0.78 ng/mL, maintaining stability under alkaline conditions (pH 10) within 1 min. In vitro CCK-8 assays confirmed that the nanocarrier effectively inhibited AGS cell proliferation in a dose-dependent manner. Furthermore, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed upregulation of BAX and modulation of hsa-miR-494, indicating a synergistic mechanism of action. These findings demonstrate the potential of I-DASA-APTMS@CP1@CB as a theranostic nanocarrier for targeted delivery and fluorescence-guided therapy of GC based on traditional Chinese medicine.