Multimodal and multiscale in vivo imaging of nanodrug body distribution and efficacy of immunomodulatory therapies.



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Project in the framework of the DFG Collaborative Research Center SFB 1066

The Collaborative Research Center (SFB)1066 investigates the use of nanoparticulate drug carriers (NP) in tumor immunotherapy. Novel polymer- and lipid-based NPs are synthesized, chemically characterized and their application in complex biological systems up to humans is investigated. The aim is to activate the immune system of tumor patients in such a way that tumors are recognized and destroyed by the body's own immune defense system. In addition to a tumor-specific immune response by vaccination, we aim in particular at an immunoreactivation of suppressed immune responses and a targeted modulation of the tumor microenvironment. Since both the selectivity and the nature of a desired immune response must be precisely controllable, requirements arise for therapeutic interventions in the immune system that cannot be met in this way by conventional small molecules as active agents. This is precisely where the potential of nanoparticulate drug carriers lies, because due to their complex - but chemically selectively modifiable - structure they can

  1. enclose active ingredients in such a way that they are protected from untargeted release or premature destruction, thus enabling the use of fragile or even toxic active ingredients (e.g. RNA, immunomodulators),
  2. transport multiple drugs simultaneously, which is often mandatory for therapeutic interventions in the immune system, and
  3. they can be modified by surface functionalization in such a way that they bind specifically to certain structures on cells or tissues and only exert their pharmacological effect there, thus enabling targeted drug delivery.

Within the framework of the SFB, we are involved with subproject Q03 in cooperation with Prof. Dr. Frank Rösch and PD Dr. Matthias Miederer. This project aims at in vivo imaging of the biodistribution of nanodimensional carriers on different length scales (from organ to cellular assembly) by PET- and optical methods. It is thereby the intention to validate fluorescence imaging against the quantitative PET method. In addition, methods to visualize the activation of the immune system (immuno-imaging) as result of the immunotherapy will be developed.