title: Delivery of Liposomal Quantum Dots via Monocytes for Imaging of Inflamed Tissue.
abstract: Quantum dots (QDs), semiconductor nanocrystals, are fluorescent nanoparticles of growing interest as an imaging tool of a diseased tissue. However, a major concern is their biocompatibility, cytotoxicity, and fluorescence instability in biological milieu, impeding their use in biomedical applications, in general, and for inflammation imaging, in particular. In addition, for an efficient fluorescent signal at the desired tissue, and avoiding systemic biodistribution and possible toxicity, targeting is desired. We hypothesized that phagocytic cells of the innate immunity system (mainly circulating monocytes) can be exploited as transporters of specially designed liposomes containing QDs to the inflamed tissue. We developed a liposomal delivery system of QDs (LipQDs) characterized with high encapsulation yield, enhanced optical properties including far-red emission wavelength and fluorescent stability, high quantum yield, and protracted fluorescent decay lifetime. Treatment with LipQDs, rather than free QDs, exhibited high accumulation and retention following intravenous administration in carotid-injured rats (an inflammatory model). QD-monocyte colocalization was detected in the inflamed arterial segment only following treatment with LipQDs. No cytotoxicity was observed following LipQD treatment in cell cultures, and changes in liver enzymes and gross histopathological changes were not detected in mice and rats, respectively. Our results suggest that the LipQD formulation could be a promising strategy for imaging inflammation.
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Gil
authors.identifier: 0000-0001-7622-9651
authors.initials: G
authors.lastname: Aizik
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Waiskopf
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Majd
authors.initials: M
authors.lastname: Agbaria
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Levi-Kalisman
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Uri
authors.identifier: 0000-0003-1698-2128
authors.initials: U
authors.lastname: Banin
authors.affiliation: Institute for Drug Research, Faculty of Medicine, ‡Institute of Chemistry and the §Institute for Life Sciences, Faculty of Life Sciences, and ∥The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 9112001, Israel.
authors.forename: Gershon
authors.initials: G
authors.lastname: Golomb
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000737:chemistry; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D007249:Inflammation / Q000000981:diagnostic imaging*; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000737:chemistry* / Q000378:metabolism*; D061848:Optical Imaging; D045663:Quantum Dots / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D051381:Rats; D011919:Rats, Inbred Strains; D018036:Selenium Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D014018:Tissue Distribution; D017967:Zinc Compounds / Q000737:chemistry
chemical_list: D019187:Cadmium Compounds; D008081:Liposomes; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; C031238:zinc sulfide
keywords: carotid injury; fluorescence imaging; inflammation; liposomes; monocytes; nanomedicine; quantum dots