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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for photodynamic therapy.
Biomaterials 2010 August
Self-quenching polysaccharide-based nanogels synthesized from pullulan/folate-pheophorbide-a (Pheo-A) conjugates were investigated for their potential to reduce photosensitizer (PS) phototoxicity in normal tissue and to enhance the efficacy of tumor treatment. While the nanogels showed photoactive properties including fluorescence and singlet oxygen generation in organic solvent (DMF), these properties were suppressed in PBS due to the self-quenching of photosensitizer moieties similar to the fluorescence resonance energy transfer (FRET) effect. When the PFP2 nanogel was co-incubated with esterase or HeLa cancer cells, its photoactivity was restored. These results demonstrate that the nanogel was internalized in cancer cells by folate receptor-mediated endocytosis and was then disintegrated by various enzymes in the lysosome, leading to restoration of photoactivity. In an in vivo study, free Pheo-A showed fluorescence immediately after injection; however, nanogel fluorescence was detected 30 min after injection, increased significantly over 12 h, and was maintained beyond 3 weeks. The phototoxic properties of the nanogel were similar to those of free Pheo-A, resulting in an IC(50) < 0.25 and apoptic cell death. Based on these results, we suggest that self-quenching PFP nanogels can be used to design new photodynamic therapies with minimal unfavorable phototoxicity.
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