Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency.
Photodynamic therapy (PDT) is a novel treatment, used mainly for anticancer therapy, that depends on the retention of photosensitizers (PS) in tumour cells and irradiation of the tumour with appropriate wavelength light. Photosensitizers are molecules such as porphyrins and chlorins that, on photoactivation, effect strongly localized oxidative damage within target cells. The PS used for PDT localize in various cytoplasmic membranous structures, but are not found in the most vulnerable intracellular sites for reactive oxygen species, such as the cell nucleus. The experimental approaches discussed in the present paper indicate that it is possible to design highly efficient molecular constructs, PS carriers, with specific modules conferring cell-specific targeting, internalization, escape from intracellular vesicles and targeting to the most vulnerable intracellular compartments, such as the nucleus. Nuclear targeting of these PS-carrying constructs results in enhanced photodynamic activity, maximally about 2500-fold that of free PS. Future work is intended to optimize this approach to the point at which tumour cells can be killed rapidly and efficiently, while minimizing normal cell and tissue damage.
Rosenkranz
A A
AA
Department of Biophysics, Biological Faculty, Moscow State University, Russian Academy of Science.
Jans
D A
DA
Sobolev
A S
AS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers; D015195:Drug Design; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy*; D019913:Nuclear Localization Signals; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D019913:Nuclear Localization Signals; D017319:Photosensitizing Agents