title: Self-quenching polysaccharide-based nanogels of pullulan/folate-photosensitizer conjugates for photodynamic therapy.
abstract: 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.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43-1 Yeokkok2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Byoung-chan
authors.initials: BC
authors.lastname: Bae
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D004950:Esterases / Q000378:metabolism; D005453:Fluorescence; D005492:Folic Acid / Q000138:chemical synthesis / Q000627:therapeutic use*; D005936:Glucans / Q000138:chemical synthesis / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000080385:Nanogels; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011094:Polyethyleneimine / Q000627:therapeutic use*; D011789:Quantum Theory; D026082:Singlet Oxygen / Q000378:metabolism; D012997:Solvents; D013997:Time Factors; D051598:Whole Body Imaging
chemical_list: D005936:Glucans; D000080385:Nanogels; D017319:Photosensitizing Agents; D012997:Solvents; C413692:polyethylene glycol polyethyleneimine nanogel; D026082:Singlet Oxygen; D011092:Polyethylene Glycols; C009109:pullulan; D011094:Polyethyleneimine; D005492:Folic Acid; D004950:Esterases