title: High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins.
abstract: Next-generation photodynamic therapy agents based upon the conjugation of multiple photosensitizers to a targeting backbone will allow for more efficacious light-based therapies. To this end, we have developed glucose-modified chlorins and bacteriochlorins featuring a reactive carboxylic acid linker for conjugation to targeting moieties. The photosensitizers were synthesized in relatively high yields from meso-tetra(p-aminophenyl)porphyrin, and resulted in neutral, hydrophilic chromophores with superb absorption profiles in the far-red and near-infrared portions of the electromagnetic spectrum. In addition, conjugation of these photosensitizers to a model nanoscaffold (crosslinked dextran-coated nanoparticles) demonstrated that the inclusion of hydrophilic sugar moieties increased the number of dyes that can be loaded while maintaining suspension stability. The described compounds are expected to be particularly useful in the synthesis of a number of targeted nanotherapeutic systems.
authors.affiliation: Center for Molecular Imaging Research, Harvard Medical School and Massachusetts General Hospital, 149 13th St., Rm 5406, Charlestown, MA 02129, USA. jason_mccarthy@hms.harvard.edu
authors.forename: Jason R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Bhaumik
authors.forename: Nabyl
authors.initials: N
authors.lastname: Merbouh
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D003432:Cross-Linking Reagents; D005947:Glucose / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis*; D011166:Porphyrins / Q000737:chemistry*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D003432:Cross-Linking Reagents; D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin; C006969:chlorin; D005947:Glucose
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