Conjugation of Bevacizumab to Cationic Liposomes Enhances Their Tumor-Targeting Potential

Abstract

Aims: Cationic liposomes have been shown to preferentially target the tumor vasculature, but not uniformly. Bevacizumab antibody selectively accumulates in tumors expressing VEGF. We thus developed bevacizumab-modified, pegylated cationic liposomes (PCLs) to improve the distribution of liposomes along tumor vessels, and to enhance tumor targeting. Materials & methods: We evaluated the delivery vehicle both in the absence and presence of VEGF, using human pancreatic cancer (Capan-1, HPAF-II and PANC-1) and endothelial (MS1-VEGF and HMEC-1) cell lines. Results: All cell lines except for HMEC-1 secreted VEGF. Modification of PCLs with bevacizumab did not alter ζ-potential, but increased overall liposome size. The toxicity profile for bevacizumab-modified PCLs was cell line dependent and, in general, bevacizumab improved cellular uptake and tumor targeting of PCLs. Conclusion: Bevacizumab-modified PCLs represent a potential improvement over the unmodified variety, supporting their future development for the treatment of cancer.

Keywords::

• anti-angiogenesis
• bevacizumab
• cancer therapy
• cationic liposomes
• drug delivery
• endothelial cells
• nanotechnology
• pancreatic cancer
• vasculature targeting

Financial & competing interests disclosure

The study was finded in part by the Provost Research and Scholarship grant awarded to Robert B Campbell. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors thank Professor Vladimir Torchilin, Department of Pharmaceutical Sciences, Northeastern University (NEU), for access to his γ-counter for biodistribution studies. This manuscript represents work submitted in partial fulfillment of the Doctoral Degree in Pharmaceutical Sciences, NEU, Boston, MA, USA (for G.M.K).

Additional information

Funding

The study was finded in part by the Provost Research and Scholarship grant awarded to Robert B Campbell. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.