Cell- and Mitochondria-Specific Fluorophores with Improved Photophysical Characteristics

In the past decade, porphyrinic pigments have been used with increasing success as photosensitizers (PSs) in photodynamic therapy (PDT) and diagnosis (PDD), which have emerged as minimally invasive regimens for the treatment and detection of cancers and pre- or non-cancerous conditions.

Evidence is mounting that the most effective photosensitizers are those with high affinities for mitochondria, which not only act as the powerhouse of the cell, but also play integral roles in the cascade of intracellular events leading to apoptosis. PDT with mitochondrial localized sensitizers promises to lead to cell death by the intrinsic apoptotic pathway. Although mitochondria are important subcellular targets for PDT-induced cell death, little is known about the structural requirements that a photosensitizer must satisfy for its selective uptake and localization in mitochondria. Thus, a more effective and selective phototherapeutic approach requires understanding how porphyrinic pigments must be designed to target and accumulate in mitochondria.

Our long-term goal is to understand how porphyrinic pigments and their metal complexes have to be designed for optimal photosensitizing activity. In this proposal, we will test the hypothesis that the design of more effective photodrugs requires their selective uptake and accumulation in mitochondria. To identify structural features and conditions that enable the selective uptake and localization of porphyrinoids and their metal complexes in mitochondria, we propose to:

I. Synthesize mitochondria-localizing porphyrinic pigments and their metal complexes.

II. Determine the ability of the porphyrinic pigments and their metal complexes to localize in mitochondria.

III. Determine the photosensitizing efficiency of the porphyrinic pigments and their metal Complexes (Humboldt University).

This aim will aid in the understanding of how the nature of the photodrug and the metal ion will define their photosensitizing and phototoxic activities. We propose to determine the photosensitizer abilities to cause oxidative damage to isolated mitochondria and cancer cells, and the photophysical and phototoxic properties of the photosensitizers in vitro.

Principal Investigators
Röder, Beate Prof. Dr. rer. nat. habil. (Details) (Experimental Physics / Photobiophysics)

Duration of Project
Start date: 11/2007
End date: 03/2011

Last updated on 2020-09-03 at 17:08