Co-delivery of icariside II and doxorubicin by self-assembled carrier-free nanofibers for anti-lung cancer therapy

Abstract

Icariside II (ICAII), a bioactive compound derived from Epimedii Folium, exhibits promising anti-tumor activity but encounters challenges in its clinical application due to its poor solubility and low bioavailability. Thus, this study developed a novel carrier-free co-delivery system of ICAII and doxorubicin (DOX) through their self-assembly into nanofibers. ICAII combined with DOX nanofibers (ICAII-DOX NFs), and ICAII-DOX/TPGS NFs (with TPGS as a stabilizer) were systematically characterized for their physicochemical properties, including size distribution, morphology, and molecular interactions. The synergistic anti-lung cancer effect of ICAII and DOX was evaluated in vitro and in vivo. The prepared ICAII-DOX NFs and ICAII-DOX/TPGS NFs showed mean sizes of 127 and 338 nm, respectively, with PDI values of 0.2–0.3 and drug loading contents of >48%. FTIR, fluorescence, NMR and X-ray powder diffraction analyses revealed that the formation of ICAII-DOX co-assembly was primarily driven by intermolecular hydrogen bonding between the two molecules. The nanofibers demonstrated controlled drug release profiles (cumulative release rate of DOX was 65.88% at 48 h, and cumulative release rate of ICAII was 74.29% at 48 h) and enhanced cellular uptake (1.8-fold more than that of the free DOX group). CCK-8 assay results showed that the IC₅₀ values (calculated in terms of DOX) of the ICAII-DOX mixture, ICAII-DOX NFs and ICAII-DOX/TPGS NFs were 0.67, 0.60 and 0.44 μM in A549 human lung carcinoma cells, respectively. In vivo studies using an A549 xenograft mouse model showed the improved therapeutic efficacy of the co-delivery system (the inhibition rate of the ICAII-DOX mixture and ICAII-DOX/TPGS NF groups was 29.90%) compared with single drug treatment (the inhibition rates of the DOX and ICAII groups were 8.70% and 17.72%, respectively). This study presents a self-assembled carrier-free co-delivery system, providing a potential strategy for treating lung cancer.