Exosome-like nanoparticles derived from Astragali Radix-Curcumae Rhizoma co-decoction enhance oral bioavailability and provide synergistic efficacy and reduced toxicity in combination with 5-fluorouracil for lung cancer therapy

The low oral bioavailability of bioactive components from the Astragali Radix-Curcumae Rhizoma herb pair severely restricts its clinical application in antitumour therapy. To address this issue, we developed a natural drug delivery system using exosome-like nanoparticles (ACELNs) isolated from the co-decoction of Astragali Radix and Curcumae Rhizoma , which can effectively encapsulate and preserve the bioactive components from the herbal pair. Systematic characterization confirmed that ACELNs maintained excellent structural integrity, flat spheroid morphology, and favorable gastrointestinal stability with desirable colloidal properties. Cellular and rat pharmacokinetic studies demonstrated that ACELNs significantly improved the oral bioavailability of the loaded active components. In Lewis lung cancer ectopic mouse model, the combination of ACELNs and 5-fluorouracil (5-FU) exhibited superior antitumour efficacy and excellent biocompatibility. This natural nanocarrier strategy provides a promising approach to overcome the bioavailability barrier of traditional Chinese medicine components and achieve synergistic therapeutic effects.