A multifunctional chitosan-silica hybrid for fluorescent LBP detection and PA2G4-targeted gallbladder cancer therapy

Gallbladder cancer (GBC) is characterized by late-stage diagnosis, high recurrence rates, and limited therapeutic options, highlighting the urgent need for novel treatment strategies. This study aims to develop a multifunctional nanoplatform for both targeted therapy and sensitive detection of Lycium barbarum polysaccharide (LBP), a natural compound with known antitumor activity but poor bioavailability. A copper-organic framework (CP1) was synthesized and covalently grafted onto chitosan via 3-chloropropyl)trimethoxysilane (CPTMS) and Compound 1 to yield 1-CS-CPTMS@CP1. Subsequent loading of LBP produced 1-CS-CPTMS@CP1@LBP, a nanocomposite with high drug-loading capacity (384.7 mg·g⁻ 1 ) and fluorescence “turn-on” sensing capability. Upon 360 nm excitation, the system exhibited a >10-fold emission increase at 620 nm in the presence of LBP, with a linear response range of 0.05-50 μM (R 1 = 0.995) and a detection limit as low as 3 nM. In vitro assays demonstrated that 1-CS-CPTMS@CP1@LBP significantly inhibited the proliferation of SGC-996 and human gallbladder cancer cell line (GBC-SD) cells more effectively than free LBP, accompanied by marked downregulation of PA2G4 mRNA, suggesting enhanced delivery and ferroptosis-related gene modulation. These findings indicate that the developed nanoplatform provides a promising dual-function strategy for LBP sensing and targeted GBC therapy.