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.