title: Enhanced growth inhibition of osteosarcoma by cytotoxic polymerized liposomal nanoparticles targeting the alcam cell surface receptor.
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.
authors.affiliation: Division 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.
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
authors.forename: Jason
authors.initials: J
authors.lastname: Chan
authors.forename: Jon O
authors.initials: JO
authors.lastname: Nagy
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Landaw
authors.forename: Katelyn
authors.initials: K
authors.lastname: McCabe
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
authors.forename: Timothy
authors.initials: T
authors.lastname: Triche
authors.forename: Hyunggyoo
authors.initials: H
authors.lastname: Kang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: James D
authors.initials: JD
authors.lastname: Marks
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Denny