Dual-functional liposomes with carbonic anhydrase IX antibody and BR2 peptide modification effectively improve intracellular delivery of cantharidin to treat orthotopic hepatocellular carcinoma mice

Xue Zhang, Congcong Lin, Waikei Chan, Kanglun Liu, Aiping LYU, Ge Lin, Rong Hu, Hongcan Shi, Hong Qi ZHANG*, Zhijun YANG

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.

Original languageEnglish
Article number3332
JournalMolecules
Volume24
Issue number18
DOIs
Publication statusPublished - 12 Sep 2019

Scopus Subject Areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

User-Defined Keywords

  • BR2 peptide
  • Cantharidin
  • Carbonic anhydrase IX
  • Dual-functionalized liposomes
  • Hepatocellular carcinoma

Fingerprint

Dive into the research topics of 'Dual-functional liposomes with carbonic anhydrase IX antibody and BR2 peptide modification effectively improve intracellular delivery of cantharidin to treat orthotopic hepatocellular carcinoma mice'. Together they form a unique fingerprint.

Cite this