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


BACKGROUND
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.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
Wenbing
W
Dai
Tingyuan
T
Yang
Yiguang
Y
Wang
Xueqing
X
Wang
Jiancheng
J
Wang
Xuan
X
Zhang
Qiang
Q
Zhang
D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
D000903:Antibiotics, Antineoplastic; D039081:Integrin alpha5beta1; D008081:Liposomes; D010455:Peptides; D004317:Doxorubicin