Abstract
We here demonstrate for the first time that 5-carboxytetramethylrhodamine (TAMRA) covalently linked to nuclear localization signal (NLS)-conjugated peptide nucleic acids (PNAs) are photosensitizers (PSs) with the capacity to initiate photochemical damage to endocytic membranes, resulting in release of endocytosed material into cytosol. Our results show that TAMRA/PNA/NLS conjugates work as multifunctional molecules by offering cellular uptake, PNA-directed gene silencing, and the possibility for targeting in a light-controlled manner. In addition to PNA-directed gene silencing, we demonstrate that TAMRA/PNA/NLS molecules may function as a PS for light-controlled release of small interfering RNA molecules from the endocytic pathway when combined with an appropriate carrier. Using these strategies, we could silence the S100A4 gene at both protein and mRNA levels in a light-controlled manner, without any detectable reduction in cell viability. Our data demonstrate the possibility for light-controlled delivery of macromolecules entrapped within endocytic vesicles using multifunctional TAMRA/PNA/NLS molecules as PSs.
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