Photopharmacology: pharmacological treatment in a new light

Samenvatting

The insufficient selectivity of drugs results from their activity other than at the intended site of action. In the human body it causes severe side effects and in the environment it leads to pollution and the development of drug resistance.
To improve drug selectivity, a new modality in medical treatment could be introduced, which uses light to control bioactivity. Photopharmacology relies on incorporating photoresponsive molecular switches into drugs. Light-induced changes in their properties are translated into a difference in the drug's activity, which can be used to render safer and more efficient treatment, enabling the local activation of an inactive drug. I have contributed significantly to the defining the field of photopharmacology and providing the proof-of-principle for the photocontrolled antibiotics and anti-cancer agents.
Photopharmacology has not yet been translated into actual clinical applications and has never been evaluated by medical imaging. In this proposal, a range of synthetic, photochemical and imaging approaches to photopharmacology will be used towards ultimately enabling highly-selective clinical treatment. The research will focus on two closely-related topics:
I) Use of various photoswitch architectures: i) Evaluating different photoswitches for their applicability in photopharmacology; ii) Applying visible- and near-IR-light-switchable moieties to allow the use of non-toxic and tissue-penetrating wavelengths of light; iii) First confirmation of localized photopharmacological treatment using PET imaging of positron-emitting photopharmaceuticals.
II) Discovery of novel photopharmaceuticals to overcome the side effects of medical treatment, with a main focus on inherently cytotoxic drugs (e.g. chemotherapeutics), used for treatment of localized diseases (e.g. solid tumors), preferably those accessible with light.
In this research, photopharmaceuticals for new therapeutic targets will be developed, with clinically-useful photochemical and pharmacological characteristics. Outside the medical field, this could lead to establishing light-controlled tools for chemical biology. In the medical field, the in-vivo application of photopharmacological therapy is ultimately envisaged within this proposal.

Producten

Wetenschappelijk artikel

  • M. J. Hansen, M. M. Lerch, W. Szymanski, B. L. Feringa, A. J. M. Driessen, W. A. Velema(2015): Ciprofloxacin–Photoswitch Conjugates: A Facile Strategy for Photopharmacology Bioconjugate Chemistry pp. 2592 - 2597
  • W. Szymanski, F. Reessing(2016): Beyond Photodynamic Therapy: Light-Activated Cancer Chemotherapy Current Medicinal Chemistry pp. asap - asap
  • G. M. van Dam, W. Szymanski, M. J. Hansen, M. M. Lerch, B. L. Feringa(2016): Emerging Targets in Photopharmacology Angewandte Chemie Inernational Edition pp. 10978 - 10999
  • M. M. Lerch, M. J. Hansen, B. L. Feringa, W. Szymanski, W. A. Velema(2016): Orthogonal photoswitching in a multifunctional molecular system Nature Communications pp. 12054 - 12054
  • W. Szymanski, M. J. Hansen, B. L. Feringa, M. M. Lerch(2016): Direct and Versatile Synthesis of Red-Shifted Azobenzenes Angewandte Chemie International Edition pp. 13514 - 13518
  • W. Szymanski, M. M. Lerch, S. J. Wezenberg, B. L. Feringa(2016): Unraveling the Photoswitching Mechanism in Donor–Acceptor Stenhouse Adducts Journal of the American Chemical Society pp. 6344 - 6347

Kenmerken

Projectnummer

723.014.001

Hoofdaanvrager

Dr. W.C. Szymanski

Verbonden aan

Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen, Radiologie

Uitvoerders

Mr. M. W. H. Hoorens MSc, N.B. Niet Bekend en Niet Gebruiken, Dr. W.C. Szymanski

Looptijd

01/11/2015 tot 31/10/2020