Development of polymeric nanoparticles for nucleic
acid formulation and delivery in vitro
and in vivo
Nanoparticles allow for the transfer of therapeutic nucleic acids (DNA/siRNA/mRNA) in vitro, in vivo and ex vivo, thus exploiting their therapeutic potential. In this context, liposomal systems as well as polymeric nanoparticles are employed.
This project focuses on establishing and further improving novel polymeric nanoparticle systems for the delivery of different types of nucleic acids. For this, novel polymers are synthesized and chemically modified, and nanoparticle formulations are optimized. For the delivery of nanoparticles into particular cell types or tissues, nanoparticles are also further modified by linking suitable antibodies.
The conditions for generating the nanoparticles are further optimized through systematic permutation of critical parameters, leading to the reproducible generation of standardized complexes with defined properties. Their physicochemical characterization includes the analysis of morphologies, determination of size and surface charge, studies on storage and stability. The biological testing includes biocompatibility and transfection efficacy and is performed in various 2D/3D in vitro/ex vivo assays. The most promising nanoparticles are further evaluated in vivo with regard to their biodistribution pattern (radioactive- and fluorescence-based methods) and toxicity. Subsequently, preclinical therapy studies are performed using selected nanoparticle formulations for the biological activity in vivo, e.g. siRNA-mediated knockdown of tumor-relevant genes in tumor xenograft mouse models. Upon explantation of the tumors, observed anti-tumor effects are comprehensively analyzed on the cellular and molecular level.
