Title:Drug Targeting Strategies for Photodynamic Therapy
Volume: 12
Issue: 5
Author(s): Frederic Schmitt and Lucienne Juillerat-Jeanneret
Affiliation:
Keywords:
Photodynamic Therapy, Drug Targeting, Peptides, Proteins, Nanoparticles, Organometallics, PHOTOSENSITIZERS, NON-PROTEIN LIGANDS, arene-ruthenium, Monoclonal Antibodies
Abstract: In human pathologies, therapeutic treatments are often limited by the lack of selectivity of drugs and their elevated effective
concentrations. Targeting these agents to a defined tissue could enhance their selectivity and then diminish their side effects when
compared to drugs that accumulate in the entire body. Targeting could also improve treatment efficiency by allowing a localized high
concentration of the agents. Based on the different behaviors and patterns of expression between diseased and normal cells, strategies for
targeting can be explored. For example, receptors, proteases or trans-membrane carriers could be different or differently expressed. Many
therapeutic procedures rely on this fact, including photodynamic therapy (PDT). PDT is already used in the treatment of some cancers, of
inflammatory diseases and others diseases such as age-related macular degeneration or acne. PDT relies on the activation of a
photosensitizer (PS) by visible light which results in the production of cytotoxic reactive oxygen species. In PDT, the general distribution
of PS to the whole body leads to generalized photosensitization and poor acceptance of treatments by patients. One way to avoid these
effects is to improve the targeting of PSs to diseased tissues using modification of PS with peptides or proteins that will target specific
receptors or enzymes. PSs could also be functionalized with non-proteic ligands such as organometalics to achieve targeted and/or
combined therapies. Alternatively, PSs could be encapsulated in nanoparticles bearing targeting agents which will decrease concentration
of free circulating PS and improve photodynamic efficiency. These different approaches will be discussed in the present review with an
emphasis on the use of peptides and proteins.