Nanoparticles for Diabetic Nephropathy Treatment

• Applicants: Professor Dr. Achim Goepferich; Professor Dr. Jens Schlossmann
• Subject Area: Pharmacy
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562750166

By 2025, the number of diabetics worldwide will rise to 700 million and almost double by 2050. Dramatic about this development is the associated striking increase in serious secondary diseases, which are based on massive damage to tissues and organs, including complete organ failure. A prominent example is diabetic nephropathy, which affects around 45% of diabetics and leads to complete filtration failure in the final stage. The main reason for this insufficiency is that the glomeruli, as the site of renal filtration, are pathophysiologically altered. Mesangial cells, which maintain the glomerular structure, show signs of pathological changes early during disease development. At present there is no drug therapy available that would be able to stop disease development. Promising drugs can either not reach mesangial cells in sufficient amounts or have severe undesirable effects. Virus-mimetic nanoparticles, that we constructed for the selective mesangial cell identification, hold the potential to close this therapeutic gap. It will be our goal to develop nanotherapeutics that allow for an efficient drug therapy in mesangial cells. The specific uptake and efficacy of nanoparticles in mesangial cells and their potential distribution to further disease relevant renal cells such as podocytes, tubular- and interstitial cells will be investigated with a mT/mG reporter mouse model, which indicates cellular nanoparticle uptake and subsequent drug release by a change of cell membrane fluorescence from red to green. Finally, we will load nanoparticles obtaining the highest efficacy with activators of soluble guanylate cyclase or proteasome inhibitors and test their effectivity in a murine model of diabetic nephropathy.

• DFG Programme: Research Grants