Chemical modification of therapeutic drugs or drug vector systems to achieve targeted therapy: looking for the grail.
Most therapeutic drugs distribute to the whole body, which results in general toxicity and poor acceptance of the treatments by patients. The targeted delivery of chemotherapeutics to defined cells, either stromal or cancer cells in cancer lesions, or defined inflammatory cells in immunological disorders, is one of the main challenges and a very active field of research in the development of treatment strategies to minimize side-effects of drugs. Disease-associated cells express molecules, including proteases, receptors, or adhesion molecules, that are different or differently expressed than their normal counterparts. Therefore one goal in the field of targeted therapies is to develop chemically derivatized drugs or drug vectors able to target defined cells via specific recognition mechanisms and also able to overcome biological barriers. This article will review the approaches which have been explored to achieve these goals and will discuss in more detail three examples (i) the use of nanostructures to take advantage of increased vascular permeability in some human diseases, (ii) the targeting of therapeutic drugs to an organ, the brain, protected against foreign molecules by the blood-brain barrier, and (iii) the use of the folate receptor to target either tumor cells or activated macrophages.
Juillerat-Jeanneret
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L
University Institute of Pathology, Bugnon 25, CH-1011 Lausanne, Switzerland. lucienne.juillerat@chuv.ch
Schmitt
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F
D001812:Blood-Brain Barrier / Q000187:drug effects; D001927:Brain Diseases / Q000188:drug therapy; D002352:Carrier Proteins / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D053758:Nanoparticles / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy; D011956:Receptors, Cell Surface / Q000187:drug effects
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface