A major limitation to using small injectable particles containing therapeutic drugs for controlled drug delivery is their quick removal from the bloodstream by mononuclear phagocytes mainly in the liver and spleen. Recent advances in how to make biodegradable nanoparticles invisible to such processes (stealth nanoparticles) using polyethylene glycol coatings have allowed for much longer circulation times which we hypothesize make possible new targeting strategies. We propose to target such stealthy drug-laden biodegradable nanoparticles to the hydroxyapatite surface of bone using covalent attachment of certain chelating groups to the surface of the nanoparticte. The drug we propose incorporating into the nanoparticle is known to protect cells from the harmful effects of chemotherapy and radiation therapy. If successful, our targeting technology could allow for selective delivery of protectant drug-containing nanoparticles to the bone whereupon biodegradation would liberate free active drug causing selectively high concentrations in the nearby contiguous bone marrow. Such selective protectant delivery to marrow could allow for more aggressive treatments of some cancers without the need for bone marrow transplants. The targeting technology proposed is a platform technology as it is amenable to substituting in other therapeutic drugs in the novel nanoparticles such as chemosensitizers or chemotherapy agents. ? ?
