Oral delivery of dextran-modified albumin nanoparticles loaded with shikonin for targeted therapy of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. METHODS: In this study, we developed a novel nanomedicine-based therapeutic approach targeting key molecules involved in the progression of CRC. By utilizing bioinformatics tools and computer simulations, we identified SLC2A1 and PKM2 as potential therapeutic targets for CRC. Through molecular docking, we confirmed that shikonin (SHK), a bioactive compound derived from traditional herbal medicine, could effectively bind to SLC2A1 and PKM2, indicating its potential therapeutic effect. The novel SHK-loaded nanoplatform, functionalized with albumin (BSA) and glycoside modification (gBSA/SHK), was designed to enhance stability and targeted delivery to tumor sites. RESULTS: In vitro and in vivo experiments showed that SHK-loaded nanoparticles exhibited good tumoricidal effects on CT26 colorectal cancer cells and shifted tumor cell metabolism. CONCLUSIONS: Overall, our results suggest that SHK-loaded nanodrugs can effectively target key molecular pathways in CRC and provide a promising strategy for colorectal cancer treatment with advantages such as improved drug stability, tumor-specific targeting, and reduced systemic toxicity.