Targeting nanoparticles for diagnosis and therapy of bone tumors: Opportunities and challenges.

A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.