Recent Improvements in the Use of Synthetic Peptides for a Selective Photodynamic Therapy

Raphael      Schneider; Loraine      Tirand; Celine      Frochot; Regis      Vanderesse; Noemie      Thomas; Julien      Gravier; Francois      Guillemin; Muriel      Barberi-Heyob

doi:10.2174/187152006778226503

Abstract

Photodynamic therapy (PDT) is a relatively new cytotoxic treatment, predominantly used in anti-cancer approaches, that depends on the retention of photosensitizers in tumor and their activation after light exposure. Photosensitizers are photoactive compounds such as porphyrins and chlorins that upon photoactivation, effect strongly localized oxidative damage within the target cells. The ability to confine activation of the photosensitizer by restricting illumination to the tumor allows for a certain degree of selectivity. Nevertheless, the targeted delivery of photosensitizers to defined cells is a major problem in PDT of cancer, and one area of importance is photosensitizer targeting. Alterations or increased levels in receptor expression of specific cellular type occur in the diseased tissues. Therefore, photosensitizers can be covalently attached to molecules such as peptides, leading to a receptor-mediated targeting strategy. These active-targeting approaches may be particularly useful for anti-vascular PDT. Moreover, it has been shown that the photocytotoxicity of photodynamic drugs could be enhanced by delivering high amounts of a photosensitizer into subcellular organelles such as the nucleus where nucleic acids represent target molecules sensitive to photodamage. The recent progresses in the use of active-targeting strategy with synthetic peptides and the interest of using an activetargeting strategy in PDT, which could allow efficient cellular internalization of photosensitizers, are described in this review.

Keywords: Photosensitizer, photodynamic therapy, synthetic peptides, targeted delivery, nuclear localization sequence

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