Tricin-Loaded Liposomes as a Passive Targeting Nanodelivery System for Enhanced Gastric Cancer Therapy

Gastric cancer (GC) has a poor prognosis. Chemotherapy causes severe systemic toxicity, and only a small subset of patients benefits from HER2/PD‑L1‑targeted therapies. Tricin (TRI), a natural flavonoid with anti‑GC activity, is limited by poor water solubility and low bioavailability. This study aimed to construct TRI‑loaded liposomes (TRI@Lips) to overcome these drawbacks and evaluate their antitumor performance. TRI@Lips were prepared by thin‑film hydration and characterized by DLS, FTIR, TEM, and release assays. Cytotoxicity, cellular uptake, in vivo tumor distribution, antitumor efficacy, and biosafety were examined using SGC‑7901/GSE‑1 cells, fluorescent tracers, and xenograft mice. TRI@Lips showed uniform spherical morphology (average size: 217.5 nm, PDI: 0.198, zeta potential: -8.84 mV), with 87.3% encapsulation efficiency, 9.2% drug loading, and 67.2% release at pH 5.0 within 72 h. The IC₅₀ against SGC‑7901 cells was 3.4 µg/mL, with minimal toxicity to GSE‑1 cells. EPR‑mediated tumor accumulation was confirmed. In vivo, TRI@Lips reduced tumor weight to 0.3 g and Ki67‑positive rate to 11.6%, without major organ injury. TRI@Lips enhance TRI solubility, cellular uptake, and tumor accumulation, representing a low‑toxic passive‑targeting candidate for GC treatment.