Conjugation of bevacizumab to cationic liposomes enhances their tumor-targeting potential.
OBJECTIVE
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.


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 zeta-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.


CONCLUSIONS
Bevacizumab-modified PCLs represent a potential improvement over the unmodified variety, supporting their future development for the treatment of cancer.
Northeastern University, 360 Huntington Avenue, Bouvé College of Health Sciences, Department of Pharmaceutical Sciences, 110 Mugar Hall, Boston, MA 02115, USA.
Geoffrey M
GM
Kuesters
Robert B
RB
Campbell
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002412:Cations; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002412:Cations; D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D011092:Polyethylene Glycols