Photoinduced effects of m-tetrahydroxyphenylchlorin loaded lipid nanoemulsions on multicellular tumor spheroids.
BACKGROUND
Photosensitizers are used in photodynamic therapy (PDT) to destruct tumor cells, however, their limited solubility and specificity hampers routine use, which may be overcome by encapsulation. Several promising novel nanoparticulate drug carriers including liposomes, polymeric nanoparticles, metallic nanoparticles and lipid nanocomposites have been developed. However, many of them contain components that would not meet safety standards of regulatory bodies and due to difficulties of the manufacturing processes, reproducibility and scale up procedures these drugs may eventually not reach the clinics. Recently, we have designed a novel lipid nanostructured carrier, namely Lipidots, consisting of nontoxic and FDA approved ingredients as promising vehicle for the approved photosensitizer m-tetrahydroxyphenylchlorin (mTHPC).


RESULTS
In this study we tested Lipidots of two different sizes (50 and 120 nm) and assessed their photodynamic potential in 3-dimensional multicellular cancer spheroids. Microscopically, the intracellular accumulation kinetics of mTHPC were retarded after encapsulation. However, after activation mTHPC entrapped into 50 nm particles destroyed cancer spheroids as efficiently as the free drug. Cell death and gene expression studies provide evidence that encapsulation may lead to different cell killing modes in PDT.


CONCLUSIONS
Since ATP viability assays showed that the carriers were nontoxic and that encapsulation reduced dark toxicity of mTHPC we conclude that our 50 nm photosensitizer carriers may be beneficial for clinical PDT applications.
Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. doris.hinger@uzh.ch.
Doris
http://orcid.org/0000-0002-4143-6674
D
Hinger
Technologies for Biology and Healthcare Division, CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), 38054, Grenoble, France.|Université Grenoble Alpes, 38000, Grenoble, France.
Fabrice
F
Navarro
Center for Microscopy and Image Analysis, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Andres
A
Käch
Technologies for Biology and Healthcare Division, CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), 38054, Grenoble, France.|Université Grenoble Alpes, 38000, Grenoble, France.
Jean-Sébastien
JS
Thomann
Technologies for Biology and Healthcare Division, CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), 38054, Grenoble, France.|Université Grenoble Alpes, 38000, Grenoble, France.
Frédérique
F
Mittler
Technologies for Biology and Healthcare Division, CEA, LETI, MINATEC Campus, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), 38054, Grenoble, France.|Université Grenoble Alpes, 38000, Grenoble, France.
Anne-Claude
AC
Couffin
Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Caroline
C
Maake
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004337:Drug Carriers / Q000008:administration & dosage; D004655:Emulsions / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008422:Materials Testing; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D008652:Mesoporphyrins; C072269:temoporfin
Biocompatibility; Lipid nanoparticles; Nanoemulsion; Photodynamic therapy; Spheroids; mTHPC