Enzymatic Digestion
Restored Photoactivity
Project Information AT A GLANCE
Project Title: Peptidic Scaffolds for Targeted Delivery of Protease-Sensitive Photosensitizer Prodrugs in Photodynamic Therapy
Project Objective: To selectively deliver fluorescent and photodynamic agents to cancer cells through proteolytic activation.
Project Duration and Timing: 36 months
Project Funding: Swiss National Science Foundation
Project Partners: • Paolo Meda (Geneva’s University Hospital)
• Nathalie Busso (Lausanne’s University Hospital)
Principle of protease mediated fluorescence detection and photodynamic therapy prodrugs. Multiple copies of a photosensitizer peptide conjugate are tethered to a polymeric carrier. Due to strong energy transfer upon irradiation with light between the photosensitizer units no fluorescence or photodynamic effect can occur. Upon encounter of a protease that recognizes the peptide sequence and digests it the photosensitizer is released from its polymeric carrier thus restoring fluorescence and photodynamic activity.
to remove the beta cell mass to assess its functionality. We hope that these contrast agents can provide a way of seeing whether these cell-based therapies are working or not.” Designing
these
molecules to perform the desired function is often only half the problem. “Molecular probes that are
used to monitor
cell imaging to the point of beginning clinical trials, offering hope for many diabetes sufferers around the world. In another very new project, researchers
“We hope that these contrast
patients iteratively need to be non-toxic, and contrast agents need to leave the body so that change can be observed over time – for example, if the contrast agent were to accumulate next to the functional beta cell mass and remain there, it would be impossible to tell whether it was there from the present injection or from a previous one.” This research is part of a large European
agents can provide a way of seeing whether these cell-based
therapies are working or not”
have developed photosensitive agents that react in the presence of proteases. “These molecules are administered into the body in an optically silent state in which they don’t fluoresce or affect the body in any way,” explains Lange. “However, as soon as they encounter certain proteases that are known to be over-expressed in cancer cells, they become optically active. We hope to use these for the treatment and detection of all types of cancer in the future.” The need for even more
project which is funded not only by the Swiss Science Foundation, but also by the FP7 programme, under the names IMIDIA and ‘Beta Image’. The latter is a 54-month- long project, which ends in March 2013, hoping to bring this new method of beta-
www.projectsmagazine.eu.com
precise and effective tools for detecting, monitoring and combatting illnesses such as cancer and diabetes is ever present, and so the work being carried out by these scientists will not only help to provide better healthcare for the patients of today, but will continue to do so in the future for as long as their work continues.
★
• Hans Acha Orbea (University of Lausanne)
Main Contact:
Norbet Lange Norbert Lange is a faculty member at the School of Pharmaceutical Sciences at University of Geneva, and a course of a continuing education program of Harvard Medical School. The work of his group is devoted to the development of new compounds and their formulation for their use in photodynamic therapy and molecular imaging. Following his PhD in Physical Chemistry obtained from the University of Göttingen (Germany) in 1995, he became interested in the use of light for the diagnosis and treatment of diseases and joined Hubert van den Bergh’s group in Lausanne. There he was implicated in the synthesis, clinical testing, and development of 5-ALA derivatives. Since then, Norbert Lange has extended his research into many fields of biophotonics. His research group is interested in the development of new concepts in photodynamic therapy, new in vivo and in vitro models, formulation of drugs, the use of nanoparticle technologies in PDT and fluorescence diagnosis, as well as molecular imaging in a clinical context.
Contact: Tel: +41 22 379 3335 Email:
Norbert.Lange@
unige.ch Web:
http://epgl.unige.ch/pharm/en/
27
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132