title: Multifunctional calcium phosphate nanoparticles for combining near-infrared fluorescence imaging and photodynamic therapy.
abstract: Photodynamic therapy (PDT) of tumors causes skin photosensitivity as a result of unspecific accumulation behavior of the photosensitizers. PDT of tumors was improved by calcium phosphate nanoparticles conjugated with (i) Temoporfin as a photosensitizer, (ii) the RGDfK peptide for favored tumor targeting and (iii) the fluorescent dye molecule DY682-NHS for enabling near-infrared fluorescence (NIRF) optical imaging in vivo. The nanoparticles were characterized with regard to size, spectroscopic properties and uptake into CAL-27 cells. The nanoparticles had a hydrodynamic diameter of approximately 200 nm and a zeta potential of around +22mV. Their biodistribution at 24h after injection was investigated via NIRF optical imaging. After treating tumor-bearing CAL-27 mice with nanoparticle-PDT, the therapeutic efficacy was assessed by a fluorescent DY-734-annexin V probe at 2 days and 2 weeks after treatment to detect apoptosis. Additionally, the contrast agent IRDye® 800CW RGD was used to assess tumor vascularization (up to 4 weeks after PDT). After nanoparticle-PDT in mice, apoptosis in the tumor was detected after 2 days. Decreases in tumor vascularization and tumor volume were detected in the next few days. Calcium phosphate nanoparticles can be used as multifunctional tools for NIRF optical imaging, PDT and tumor targeting as they exhibited a high therapeutic efficacy, being capable of inducing apoptosis and destroying tumor vascularization.
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, 07747 Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Haedicke
authors.affiliation: Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, 45117 Essen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Kozlova
authors.affiliation: Biolitec Research GmbH, Research & Development, 07745 Jena, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, 07747 Jena, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgräber
authors.affiliation: Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, 45117 Essen, Germany. Electronic address: matthias.epple@uni-due.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Epple
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Friedrich-Schiller University Jena, 07747 Jena, Germany. Electronic address: Ingrid.Hilger@med.uni-jena.de.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002130:Calcium Phosphates / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005453:Fluorescence; D006801:Humans; D007259:Infrared Rays; D008027:Light; D008163:Luminescent Measurements; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000494:pharmacology; D010778:Photochemotherapy; D012542:Scattering, Radiation; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D002130:Calcium Phosphates; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C020243:calcium phosphate
keywords: Apoptosis; Calcium phosphate nanoparticles; NIRF optical imaging; Photodynamic therapy; Vascularization