Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide

Congcong Lin, Xue Zhang, Hubiao CHEN, Zhaoxiang BIAN, Ge ZHANG, Muhammad Kashif Riaz, Deependra Tyagi, Ge Lin, Yanbo Zhang, Jinjin Wang, Aiping LYU, Zhijun YANG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

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-TPL-lip 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.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalDrug Delivery
Volume25
Issue number1
DOIs
Publication statusPublished - 15 Jan 2018

Scopus Subject Areas

  • Pharmaceutical Science

User-Defined Keywords

  • Carbonic anhydrase IX
  • Dual-ligand liposomes
  • Orthotopic lung cancer model
  • Pulmonary delivery
  • Tumor lineage-homing cell penetrating peptide

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