title: Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer.
abstract: BACKGROUND
  Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution.
  
  
  METHODS
  AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice.
  
  
  RESULTS
  The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1h, 24h and 48h) post iv. administration.
  
  
  CONCLUSIONS
  The AlPc-based copolymer nanoparticles developed offer potential as a single agent-multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics.
authors.affiliation: Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, NOVUM, Karolinska Institutet (KI), Stockholm, Sweden; Department of Materials Science, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt; Functional Materials Division (FNM), Department of Materials and Nanophysics, Royal Institute of Technology (KTH), Stockholm, Sweden.
authors.forename: Heba
authors.initials: H
authors.lastname: Asem
authors.affiliation: Department of Materials Science, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt.
authors.forename: Ahmed Abd
authors.initials: AA
authors.lastname: El-Fattah
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
authors.forename: Noha
authors.initials: N
authors.lastname: Nafee
authors.affiliation: Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, NOVUM, Karolinska Institutet (KI), Stockholm, Sweden; Pancreatic Cancer Research Laboratory, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
authors.forename: Labiba
authors.initials: L
authors.lastname: Khalil
authors.affiliation: Functional Materials Division (FNM), Department of Materials and Nanophysics, Royal Institute of Technology (KTH), Stockholm, Sweden.
authors.forename: Mamoun
authors.initials: M
authors.lastname: Muhammed
authors.affiliation: Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, NOVUM, Karolinska Institutet (KI), Stockholm, Sweden; Clinical Research Center (KFC), NOVUM, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Electronic address: Moustapha.Hassan@ki.se.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.affiliation: Department of Materials Science, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, Egypt.
authors.forename: Sherif
authors.initials: S
authors.lastname: Kandil
mesh_terms: D000818:Animals; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D007211:Indoles / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D007211:Indoles; D053769:Nanocapsules; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011091:Polyesters; D013501:Surface-Active Agents; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D011092:Polyethylene Glycols; C060570:aluminum phthalocyanine
keywords: Aluminum phthalocyanine; Biodistribution; Copolymer; Imaging; Nanoparticles; Nanophotosensitizer