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

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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: