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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.
AuthorsKaoru Nishikawa, Tomohiro Asai, Hirokazu Shigematsu, Kosuke Shimizu, Hisakazu Kato, Yoshihiro Asano, Seiji Takashima, Eisuke Mekada, Naoto Oku, Tetsuo Minamino
JournalJournal 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
PMID22020380 (Publication Type: Journal Article)
CopyrightCopyright © 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)
  • Cercopithecus 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

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