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 from Epimedii Folium, exhibits promising anti-tumor activity but faces challenges in clinical application due to poor solubility and low bioavailability. This study developed a novel carrier-free co-delivery system of ICAII and doxorubicin (DOX) through self-assembly into nanofibers. The 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 both 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 > 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 (DOX’s cumulative release rate was 65.88% at 48 h, and ICAII’s cumulative release rate was 74.29% at 48 h) and enhanced cellular uptake (1.8-fold more than free DOX group). CCK-8 assay results showed that the IC50 (calculated in term of DOX) of ICAII-DOX mixture, ICAII-DOX NFs and ICAII-DOX/TPGS NFs were 0.67, 0.60 and 0.44 μM on A549 human lung carcinoma cells. In vivo studies using an A549 xenograft mouse model showed improved therapeutic efficacy (the inhibition rates of ICAII-DOX Mixture and ICAII-DOX/TPGS NFs groups were 29.90%) compared to single drug treatment (the inhibition rates of DOX and ICAII groups were 8.70% and 17.72%). This study presents a self-assembled carrier-free co-delivery system, providing a potential strategy for treating lung cancer.