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Sarcoma
Volume 2012 (2012), Article ID 126906, 11 pages
http://dx.doi.org/10.1155/2012/126906
Research Article

Enhanced Growth Inhibition of Osteosarcoma by Cytotoxic Polymerized Liposomal Nanoparticles Targeting the Alcam Cell Surface Receptor

1Division of Pediatric Hematology/Oncology, Department of Pediatrics, Mattel Children's Hospital and Gwynne Hazen Cherry Memorial Laboratories, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095-1781, USA
2NanoValent Pharmaceuticals Inc., Bozeman, MT 59718-4012, USA
3Department of Biomathematics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1766, USA
4Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, UCLA, Los Angeles, CA 90095-1770, USA
5Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA
6Department of Anesthesia and Perioperative Cave, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94110, USA

Received 5 June 2012; Accepted 3 July 2012

Academic Editor: Norman Jaffe

Copyright © 2012 Noah Federman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Osteosarcoma is the most common primary malignancy of bone in children, adolescents, and adults. Despite extensive surgery and adjuvant aggressive high-dose systemic chemotherapy with potentially severe bystander side effects, cure is attainable in about 70% of patients with localized disease and only 20%–30% of those patients with metastatic disease. Targeted therapies clearly are warranted in improving our treatment of this adolescent killer. However, a lack of osteosarcoma-associated/specific markers has hindered development of targeted therapeutics. We describe a novel osteosarcoma-associated cell surface antigen, ALCAM. We, then, create an engineered anti-ALCAM-hybrid polymerized liposomal nanoparticle immunoconjugate ( 𝛼 -AL-HPLN) to specifically target osteosarcoma cells and deliver a cytotoxic chemotherapeutic agent, doxorubicin. We have demonstrated that 𝛼 -AL-HPLNs have significantly enhanced cytotoxicity over untargeted HPLNs and over a conventional liposomal doxorubicin formulation. In this way, 𝛼 -AL-HPLNs are a promising new strategy to specifically deliver cytotoxic agents in osteosarcoma.