School of Chinese Medicine
The abilities of a drug delivery system to target and penetrate tumor masses are key factors in determining the system’s chemotherapeutic efficacy. Here, we explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to simultaneously enhance the tumor-specific targeting and increase tumor cell penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in CA IX-positive lung cancer cells, which showed tunable size (137.6 ± 0.8 nm), high-encapsulation efficiency (86.3 ± 2.6%) and sustained release. Dl-TPLlip significantly improved the ability of liposomes to penetrate 3 D tumor spheroids and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies in rats that received TPL liposomal formulations by endotracheal administration showed a reduced concentration of TPL (17.3%–30.6% compared to free TPL) in systemic circulation. After pulmonary administration in orthotopic lung tumor-bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents a potential system for localized and targeted delivery of anti-cancer drugs to improve their efficacy.
Dual-ligand liposomes, carbonic anhydrase IX, tumor lineage-homing cell penetrating peptide, pulmonary delivery, orthotopic lung cancer model
Source Publication Title
Taylor & Francis
Link to Publisher's Edition
Lin, C., Zhang, X., Chen, H., Bian, Z., Zhang, G., Riaz, M., Tyagi, D., Lin, G., Zhang, Y., Wang, J., Lu, A., & Yang, Z. (2018). Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide. Drug Delivery, 25 (1), 256-266. https://doi.org/10.1080/10717544.2018.1425777