Journal
DRUG DELIVERY
Volume 25, Issue 1, Pages 256-266Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2018.1425777
Keywords
Dual-ligand liposomes; carbonic anhydrase IX; tumor lineage-homing cell penetrating peptide; pulmonary delivery; orthotopic lung cancer model
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Funding
- University Grants Committee of Hong Kong for the General Research Fund [GRF/RGC] [12102514-HKBU: 32-14-125]
- Hong Kong Baptist University Faculty Research Grant [FRG2/15-16/078]
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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 +/- 0.8nm), high-encapsulation efficiency (86.3 +/- 2.6%) and sustained release. Dl-TPL-lip significantly improved the ability of liposomes to penetrate 3D 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.
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