Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer.

Abstract

Increased expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) is frequently observed in certain cancers such as ovarian and breast cancers, and this protein is a desirable target for drug delivery by a drug delivery system (DDS). In the present study, we developed novel immunoliposomes targeting HB-EGF for cancer therapy. The immunoliposomes significantly associated with Vero-H cells overexpressing HB-EGF compared with their binding to wild-type Vero cells, whereas liposomes without modification by the antibody did not associate with either type of cells. Moreover, enhanced uptake of the immunoliposomes into Vero-H cells was observed as well as that into MDA-MB-231 human breast cancer cells, which are known to highly express HB-EGF. These results suggest that HB-EGF mediates the binding and uptake of the immunoliposomes in HB-EGF-expressing cells. Next, we determined the therapeutic effect of these immunoliposomes encapsulating an anticancer drug on tumor-bearing mice. For this purpose, we prepared doxorubicin (DOX)-encapsulated immunoliposomes and injected them intravenously into mice bearing MDA-MB-231 cancer cells. As a result, these DOX-encapsulated immunoliposomes suppressed not only tumor progression but also tumor regression. In conclusion, our results indicate that anti-HB-EGF antibody-modified liposomes could be a useful DDS carrier for the treatment of HB-EGF-expressing cancers.

• Authors: Kaoru Nishikawa, Tomohiro Asai, Hirokazu Shigematsu, Kosuke Shimizu, Hisakazu Kato, Yoshihiro Asano, Seiji Takashima, Eisuke Mekada, Naoto Oku, Tetsuo Minamino
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 160 Issue 2 Pg. 274-80 (Jun 10 2012) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 22020380 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Drug Carriers
• HBEGF protein, human
• Hbegf protein, mouse
• Heparin-binding EGF-like Growth Factor
• Immunoglobulin Fab Fragments
• Immunoglobulin G
• Intercellular Signaling Peptides and Proteins
• Liposomes
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, therapeutic use)
• Blotting, Western
• Cell Proliferation (drug effects)
• Chlorocebus aethiops
• Doxorubicin (administration & dosage, therapeutic use)
• Drug Carriers (chemistry)
• Female
• Heparin-binding EGF-like Growth Factor
• Humans
• Immunoglobulin Fab Fragments (chemistry, immunology)
• Immunoglobulin G (chemistry, immunology)
• Intercellular Signaling Peptides and Proteins (biosynthesis, metabolism)
• Liposomes
• Mammary Neoplasms, Experimental (drug therapy, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Protein Binding
• Real-Time Polymerase Chain Reaction
• Vero Cells
• Xenograft Model Antitumor Assays