Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis melanoma

J Transl Med. 2013 Apr 3:11:86. doi: 10.1186/1479-5876-11-86.

Abstract

Background: The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo.

Method: We designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis.

Results: We found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone.

Conclusion: The present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cations
  • Eye Proteins / genetics*
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Immunoglobulin G / chemistry
  • Liposomes / chemistry
  • Liposomes / metabolism*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy*
  • Melanoma / pathology*
  • Melanoma / therapy*
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Nerve Growth Factors / genetics*
  • Serpins / genetics*

Substances

  • Cations
  • Eye Proteins
  • Immunoglobulin G
  • Liposomes
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor