Multifunctional lipid nanoparticles
About
Our resear focuses on the development of lipid-based nanoparticles as universal carriers for biomacromolecules such as mRNA, proteins, or anti-aging polyphenols, used in medical applications.
Research Topics
Delivery of biomolecules to living cells is a crucial step in pharmacological treatments and in most life science experiments. Lipid nanoparticles (LNP) are widely used for this purpose based on their high bioavailability and low toxicity. The main drawback of such liposomes is that their cellular uptake shows a strong preference for endocytosis. A faster and more effective alternative for efficient molecular delivery is the induction of membrane fusion between the nanoparticle and the mammalian cell membranes. Moreover, molecular delivery by fusion completely bypasses endosomes, avoiding cargo degradation. For this reason we developed lipid-based nanoparticles with high fusogenic character as universal carriers for biomolecules. We efficiently incorporated lipids, proteins, and mRNA into mammalian cells. The interaction of those particles with the cargo molecules, as well as with the surrounding body fluid (blood serum) or basal membranes are also in our research focus. Moreover, new pharmacological strategies have been developed for the activation of immune cells against cancer cells improving cancer therapy efficiency. Our actual study focuses on the targeted incorporation of polyphenols against radical oxygen species into the cerebral microvasculature of rodents to improve age-related cognitive impairments.
Projects
Deciphering the phase behavior of fusogenic LNPs
Development of molecular delivery carriers for in vitro and in vivo applications
Targeted delivery of polyphenols through the blood brain barrier
Selected Publications
1. Wiedenhoeft, Braun, Springer, Teske, Noetzel, Merkel, and Csiszár (2020) The Basement Membrane in a 3D Breast Acini Model Modulates Delivery and Anti-Proliferative Effects of Liposomal Anthracyclines. Pharmaceuticals 13(9), 256
2. Hoffmann, Hersch, Merkel, Csiszar, Hoffmann (2019) Changing the way of entrance: highly efficient transfer of mRNA and siRNA via fusogenic nanocarriers, J of Biomed Nanotech. 15: 1-14
3. Wiedenhoeft, Tarantini, Nyúl-Tóth, Yabluchanskiy, Csipo, Balasubramanian, Lipecz, Kiss, Csiszár, Csiszar, Ungvari (2019) Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice. Geroscience, 41(6): 711
4. Kube, Hersch, Naumovska, Gensch, Hendriks, Franzen, Landvogt, Siebrasse, Kubitscheck, Hoffmann, Merkel, Csiszár (2017) Fusogenic Liposomes as Nanocarriers for Delivery of Intracellular Proteins, Langmuir 33: 1051
5. Csiszár, Hersch, Dieluweit, Biehl, Merkel, and Hoffmann (2010) Novel Fusogenic Liposomes for Fluorescent Cell Labeling and Membrane Modification, Bioconjugate Chemistry21: 537-543