drug delivery; NMR-spectroscopy; photosensitizers; cells; biocompatible nanoparticles; chlorin; photodynamic therapy; Magic angle spinning; photosensitizers
Pfister Sara, Sauser Luca, Gjuroski Ilche, Furrer Julien, Vermathen Martina (2019), Monitoring the encapsulation of chlorin e6 derivatives into polymer carriers by NMR spectroscopy, in Journal of Porphyrins and Phthalocyanines
, 23(11n12), 1576-1586.
Gjuroski Ilche, Girousi Eleftheria, Meyer Christoph, Hertig Damian, Stojkov Darko, Fux Michaela, Schnidrig Nicolas, Bucher Jan, Pfister Sara, Sauser Luca, Simon Hans-Uwe, Vermathen Peter, Furrer Julien, Vermathen Martina (2019), Evaluation of polyvinylpyrrolidone and block copolymer micelle encapsulation of serine chlorin e6 and chlorin e4 on their reactivity towards albumin and transferrin and their cell uptake, in Journal of Controlled Release
, 316, 150-167.
Vermathen Martina, Müller Joachim, Furrer Julien, Müller Norbert, Vermathen Peter (2018), 1 H HR-MAS NMR spectroscopy to study the metabolome of the protozoan parasite Giardia lamblia, in Talanta
, 188, 429-441.
Gjuroski Ilche, Furrer Julien, Vermathen Martina (2018), How Does the Encapsulation of Porphyrinic Photosensitizers into Polymer Matrices Affect Their Self-Association and Dynamic Properties?, in ChemPhysChem
, 19(9), 1089-1102.
Vermathen Martina, Diserens Gaëlle, Vermathen Peter, Furrer Julien (2017), Metabolic Profiling of Cells in Response to Drug Treatment using 1 H High-resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy, in CHIMIA International Journal for Chemistry
, 71(3), 124-129.
Diserens G., Hertig D., Vermathen M., Legeza B., Flück C. E., Nuoffer J.M., Vermathen P. (2017), Metabolic stability of cells for extended metabolomical measurements using NMR. A comparison between lysed and additionally heat inactivated cells, in The Analyst
, 142(3), 465-471.
Diserens Gaëlle, Vermathen Martina, Gjuroski Ilche, Eggimann Sandra, Precht Christina, Boesch Chris, Vermathen Peter (2016), Direct determination of phosphate sugars in biological material by 1H high-resolution magic-angle-spinning NMR spectroscopy, in Analytical and Bioanalytical Chemistry
, 408(20), 5651-5656.
Hädener Marianne, Gjuroski Ilche, Furrer Julien, Vermathen Martina (2015), Interactions of Polyvinylpyrrolidone with Chlorin e6-Based Photosensitizers Studied by NMR and Electronic Absorption Spectroscopy, in The Journal of Physical Chemistry B
, 119(36), 12117-12128.
Vermathen Martina, Paul Lydia E. H., Diserens Gaëlle, Vermathen Peter, Furrer Julien (2015), 1H HR-MAS NMR Based Metabolic Profiling of Cells in Response to Treatment with a Hexacationic Ruthenium Metallaprism as Potential Anticancer Drug, in PLOS ONE
, 10(5), e0128478-e0128478.
BackgroundPhotodynamic Therapy (PDT) is based on the light triggered toxicity of photosensitizers (PSs), mainly porphyrinic compounds, accumulating in diseased tissue. PDT is thus a highly selective, minimally invasive treatment modality and as such recognized as promising alternative to conventional cancer therapy. Following the early success of Hematoporphyrin and Photofrin® numerous differently structured 2nd generation porphyrinic PSs have been designed. However, poor water solubility and self-association of porphyrinic PSs under physiologic conditions are still the main limitations of PDT and the reason for the yet small number of clinically approved PDT drugs. Therefore, the development of suitable carrier systems for the most promising PSs like amino acid conjugates of chlorin e6 will allow overcoming these problems thereby making a big step towards successful PDT applications. In particular, the use of biocompatible nanoparticles (NPs) has become a focus of current research in the field of PDT. To date, the number of such 3rd generation PSs associated with NPs is still very limited as is the understanding of NP uptake and interactions with cells. Nevertheless, the entry of PDT into nanomedicine is currently considered the most promising approach towards clinical approval of PDT drugs. Objective The proposed research project is designed as continuation of our previous NMR spectroscopic studies characterizing aggregation behavior and membrane interactions of porphyrinic compounds including amino acid conjugates of chlorin e6. The main goals of this proposal are: A) Preparation of nanoparticles composed of biocompatible block copolymers as carrier systems tailored for encapsulation of amino acid derivatives of chlorin e6. The NP formulation is aimed at preventing self-association of the chlorin compounds, enhancing their stability, cell uptake and intracellular phototoxicity which ultimately will lead to increased PDT efficacy and prospect of clinical approval. Liquid state NMR spectroscopy will be applied as powerful tool providing both, structural and dynamic information, to monitor the encapsulation process and determine the most relevant properties like payload or release rate of the chlorin-carrier systems.B) Application of fluorescence techniques as complementary tool to monitor cell uptake, intracellular localization and photophysical properties of internalized PSs which will help to estimate the synergic effect of the carrier system.C) As new approach in the field of PDT research, High Resolution Magic angle spinning (HR-MAS) NMR spectroscopy will be employed to study the cellular metabolic response to the treatment with pure and NP-encapsulated PS. Moreover, HR-MAS will be applied to monitor the phototoxic reaction following light irradiation.Importance and impactThe design of optimized biocompatible NPs for amino acid conjugates of chlorin e6 will leverage the prospect of clinical approval of these promising PDT drugs. The systems will likewise be transferrable to structurally related PSs thus contributing to improved drug design and better prediction of the treatment outcome. Combining NMR spectroscopy which provides insights into submolecular structural and dynamic properties with fluorescence techniques for photophysical characterization will provide a comprehensive picture of the newly developed PS-NP systems. In particular, the novel approach of HR-MAS NMR applied to living cells will contribute to a better understanding of the mechanisms involved in NP assisted PDT including interactions with cells and cellular uptake.