Synthesis and Functionalization of Nanoparticles
This effort will be dedicated to purpose-driven production of functional nanocarriers with defined composition, size, shape and surface-rooted linker groups. For this purpose, non-hazardous and FDA-approved nanoscopic carriers (Magnetite, Fe3O4; Silica, SiO2) will be covalently attached to oligonucleotides and peptides using cross-condensation or click-chemistry routes. Validation of synthetic protocols and ensuring the reproducibility of conjugation behavior (fusion of inorganic carrier and biomolecules) will be targeted within this work package.
Engineered Biomolecular Conjugates
Evaluation of Nanocarrier-based RNA Transport and Tracking
Furthermore, the bio-distribution and tumor suppressive function of the constructs will be evaluated on already established mouse models by monitoring tumor growth with micro-computer tomography (μCT) and serial magnetic resonance imaging (MRI). Moreover, changes in proliferation, apoptosis and oncogenic pathways will be studied histologically, immunohistologically and by means of the molecular genetic tools (qPCR).
Function of RNA-nanocarrier conjugates for extracting and detecting circulating miRNAs from body fluids will be studied in urine samples of patients with chronic kidney disease or renal cancer.
Establishment and Coordination of an Interactive Network
Through the forum activities, our interdisciplinary network, focusing on approaches of nanocarrier-based therapeutics and diagnostics, will be expanded to define an interdisciplinary scientific environment and provide a new platform for exchange of ideas. We will exchange students in lab rotations, organize a regular seminar series and invite speakers from different disciplines covering i) RNA structural
chemistry and capture technology as well as application of RNA targets as biomarker molecules, ii) imaging and quality control of RNA-Peptide macromolecular conjugates iii) pharmacological
bioassays and iv) clinical application of nanotherapeutics and –diagnostics.