Chemie | Biochemie | Medizin
Xeno Messmer, 2005 | Bern, BE
In photodynamic therapy (PDT), singlet and radical oxygen species are generated within the cytoplasm of cells in the presence of light, a photosensitizing molecule and oxygen to destroy cancer cells selectively. The use of porphyrinic structures (PS) as photosensitizers holds promise for targeting cancer cells. However, direct incorporation of the porphyrins into cancer cells remains elusive. To facilitate the permeation of the photosensitizers, Dr. Martina Vermathen’s research group introduced specific phospholipid nanocarriers for topical porphyrin application, potentially destroying skin cancer cells from within. The nanocarriers, also known as bicelles, contain short- and long-chain lipids forming membranous discs with micellular and liposomal properties. However, since a sufficiently high enough concentration of PS in the cancer cells has not yet been clinically achieved, the goal of this study was to further improve skin uptake of the nanocarriers.
Introduction
Two approaches were tested to enhance skin uptake: (1) comparing polar and nonpolar porphyrins and (2) assessing the effect of a penetration enhancer, DMSO, through a neat and diluted application.
Methods
The polarity of the porphyrins was first quantified with a log P test. The bicelles were then assembled by incorporating two different PS compounds, either the mono- or tetra-4-carboxy substituted phenyl porphyrin. They were then characterized by 1D and 2D-NMR analysis, (i.e., 1H, 1H1H NOESY, and 1H DOSY spectroscopy). The porphyrin permeation was tested by Franz diffusion tests on pig ear skin. For the second approach, DMSO was added in the Franz diffusion test, either directly applied on the skin (“neat application”) or diluted in the bicelles constructs (“diluted application”).
Results
The log P test for the mono- and the tetra-carboxyphenyl porphyrin resulted in a value of 4.5 and -1.1, respectively. The more polar tetra-carboxyphenyl porphyrin exhibited 2.8 times better skin uptake compared to the mono-carboxyphenyl porphyrin, while the neat DMSO application increased uptake by a factor of 5.5. The diluted DMSO application did not show improvements and even worsened skin uptake slightly. Analytical techniques revealed differences in porphyrin encapsulation and skin penetration: The mono-carboxyphenyl porphyrins were potentially encapsulated in the centre of the bicelles, whereas tetra-carboxyphenyl porphyrins were rather localised around the nanocarriers.
Discussion
Results indicated potential instability of bicelles constructs. The more polar tetra-substituted porphyrins showed superior skin diffusion than the mono-substituted derivative, favouring epidermal localisation, advantageous for non-melanoma skin cancer. The neat DMSO application facilitated enhanced skin uptake by inducing membrane destabilization and pore formation but may have limited applicability.
Conclusions
Further research is suggested to explore porphyrinic PS with alternative polar substitution patterns and tailored penetration enhancers for lipid-based delivery systems. Overall, the study underscores the importance of molecular properties of the PS system and delivery strategies in optimizing PDT for skin cancer treatment.
Würdigung durch den Experten
Dr. Rolf Schütz
Das komplexe Thema wurde dank der realistischen Zielsetzung und wertvollen Unterstützung durch die Forschungsgruppe in eine sinnvolle Arbeit umgesetzt. Sie führte zu greifbaren Ergebnissen und nützlichen Schlussfolgerungen, die als Grundlage für Folgearbeiten dienen. Xeno Messmer ist eine klare wissenschaftliche Vorgehensweise gelungen, die durch sorgfältig ausgeführte Arbeitsabläufe und den professionellen Bericht auf hohem sprachlichem Niveau geprägt ist. Seine runde Arbeit überzeugt durch die Struktur und Resultate sowie durch ein besonderes Mass an Reife für die wissenschaftliche Praxis.
Prädikat:
hervorragend
Sonderpreis «Taiwan International Science Fair (TISF)» gestiftet von den Odd Fellows, Helvetia Loge Nr. 1
Gymnasium Kirchenfeld, Bern
Lehrer: Dr. Martin Lanz
