title: Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and tolerance in CAL-33 tumor bearing nude mice.
abstract: BACKGROUND
  Photodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor. However, a routine use is hindered by the PS's poor water solubility and extended cutaneous photosensitivity of patients after treatment. In our study we sought to overcome these limitations by encapsulation of the PS m-tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots).
  
  
  RESULTS
  In CAL-33 tumor bearing nude mice we compared the Lipidots to the existing liposomal mTHPC nanoformulation Foslip and the approved mTHPC formulation Foscan. We established biodistribution profiles via fluorescence measurements in vivo and high performance liquid chromatography (HPLC) analysis. All formulations accumulated in the tumors and we could determine the optimum treatment time point for each substance (8 h for mTHPC, 24 h for Foslip and 72 h for the Lipidots). We used two different light doses (10  and 20 J/cm2) and evaluated immediate PDT effects 48 h after treatment and long term effects 14 days later. We also analyzed tumors by histological analysis and performing reverse transcription real-time PCR with RNA extracts. Concerning tumor destruction Foslip was superior to Lipidots and Foscan while with regard to tolerance and side effects Lipidots were giving the best results.
  
  
  CONCLUSIONS
  We could demonstrate in our study that nanoformulations are superior to the free PS mTHPC. The development of a potent nanoformulation is of major importance because the free PS is related to several issues such as poor bioavailability, solubility and increased photosensibility of patients. We could show in this study that Foslip is very potent in destroying the tumors itself. However, because the Lipidots' biocompatibility is outstanding and superior to the liposomes we plan to carry out further investigations and protocol optimization. Both nanoformulations show great potential to revolutionize PDT in the future.
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland. doris.hinger@uzh.ch.
authors.forename: Doris
authors.identifier: http://orcid.org/0000-0002-4143-6674
authors.initials: D
authors.lastname: Hinger
authors.affiliation: Biolitec Research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.affiliation: CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Technologies for Biology and Healthcare Division, 38054, Grenoble, France.|Université Grenoble Alpes, Grenoble, 38000, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Navarro
authors.affiliation: Department of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Spingler
authors.affiliation: Department of Inorganic Chemistry, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
authors.forename: Devaraj
authors.initials: D
authors.lastname: Pandiarajan
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Frauenklinikstrasse 24, Zurich, 8091, Switzerland.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Walt
authors.affiliation: CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Technologies for Biology and Healthcare Division, 38054, Grenoble, France.|Université Grenoble Alpes, Grenoble, 38000, France.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Couffin
authors.affiliation: Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Maake
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004655:Emulsions / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004655:Emulsions; D008081:Liposomes; D017319:Photosensitizing Agents
keywords: Head and neck cancer; Liposome; Nanoemulsion; PDT; mTHPC