Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy

Sci Rep. 2017 Apr 20;7(1):1097. doi: 10.1038/s41598-017-00957-4.

Abstract

Antibody-decorated liposomes can facilitate the precise delivery of chemotherapeutic drugs to the lung by targeting a recognition factor present on the surface of lung tumor cells. Carbonic anhydrase IX (CA IX) is an enzyme expressed on the surface of lung cancer cells with a restricted expression in normal lungs. Here, we explored the utility of anti-carbonic anhydrase IX (CA IX) antibody, conjugated to the surface of triptolide (TPL)-loaded liposomes (CA IX-TPL-Lips), to promote the therapeutic effects for lung cancer via pulmonary administration. It was found that the CA IX-TPL-Lips significantly improved the cellular uptake efficiency in both CA IX-positive human non-small cell lung cancer cells (A549) and A549 tumor spheroids, resulting in the efficient cell killing compared with free TPL and non-targeted TPL-Lips. In vivo, CA IX-Lips via pulmonary delivery showed specificity and a sustained release property resided up to 96 h in the lung, both of which improved the efficiency of TPL formulations in restraining tumor growth and significantly prolonged the lifespan of mice with orthotopic lung tumors. The results suggest that CA IX-decorated liposomes can potentially be used as an effective therapeutic strategy for lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antigens, Neoplasm / administration & dosage*
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Carbonic Anhydrase IX / administration & dosage*
  • Carbonic Anhydrase IX / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Cell Line, Tumor
  • Diterpenes / administration & dosage*
  • Drug Delivery Systems / methods
  • Epoxy Compounds / administration & dosage
  • Humans
  • Liposomes
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Male
  • Mice, Inbred BALB C
  • Phenanthrenes / administration & dosage*

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Immunological
  • Diterpenes
  • Epoxy Compounds
  • Liposomes
  • Phenanthrenes
  • triptolide
  • CA9 protein, human
  • Carbonic Anhydrase IX