Peptide PHSCNK as an integrin α5β1 antagonist targets stealth liposomes to integrin-overexpressing melanoma.

Abstract

As an integrin α(5)β(1) antagonist, N-acetyl-proline-histidine-serine-cysteine-asparagine-amide (Ac-PHSCN-NH(2)) is currently in phase II trials for various cancer therapies. In this study Ac-PHSCNK-NH(2) (PHSCNK) was used as a novel homing peptide to prepare ligand-targeted liposomes loaded with doxorubicin (PHSCNK-PL-DOX), with the hypothesis that the therapy target of integrin α(5)β(1) may also serve as a delivery target. The stealth liposomes loaded with doxorubicin (PL-DOX) were used as the control. PHSCNK-PL-DOX demonstrated an enhanced intracellular uptake and a greater cytotoxicity against melanoma B16F10 cells in comparison with PL-DOX. The novel targeted formulation displayed stronger tumor inhibition and prolonged survival time in comparison with controls in C57BL/6 mice bearing B16F10 tumors, and it exhibited less heart toxicity in hematoxylin-eosin (H&E) staining of tissues. Taking the pharmacokinetics and biodistribution results into account, the authors conclude that α(5)β(1) integrin-mediated liposomes might be used as a potential delivery system for targeted tumor therapy.

FROM THE CLINICAL EDITOR:

Lactosyl-norcantharidin TMC nanoparticles were found superior in comparison with Lac-NCTD and Lac-NCTD chitosan nanoparticles from the standpoint of antitumor activity on murine hepatocarcinoma 22 subcutaneous model.

• Authors: Wenbing Dai, Tingyuan Yang, Yiguang Wang, Xueqing Wang, Jiancheng Wang, Xuan Zhang, Qiang Zhang
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 8 Issue 7 Pg. 1152-61 (Oct 2012) ISSN: 1549-9642 [Electronic] United States
• PMID: 22306158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Integrin alpha5beta1
• Liposomes
• Peptides
• Doxorubicin

Topics

• Amino Acid Sequence
• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, pharmacokinetics, therapeutic use)
• Drug Delivery Systems
• Integrin alpha5beta1 (antagonists & inhibitors, genetics, metabolism)
• Liposomes (chemistry, metabolism)
• Melanoma (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Peptides (chemistry, metabolism)
• Up-Regulation