Our department has been involved in applied reseach for long time, in the field of photodynamic therapy of tumors, for which we were awarded by two patents of European Patent Office, No. EP 18822125.3 and EP 07817403.4. Currently, we use our previous opinion with nanoparticle photophysics and pharmacology in order to develop paramagnetic nanoparticles conjugated with modified GLP-1 peptide for semi-quantification of β cell mass in vivo in rodent pancreatic islets. The development proceeds in collaboration with the Department of Polymeric Particles, Institute of Macromolecular Chemistry (Ing. Daniel Horák, CSc and Oleg Shapoval, PhD) and the Magnetic Resonance Department of IKEM (The Institute of Clinical and Experimental Medicine, Ing. Daniel Jirák, PhD).
The liraglutide (a GLP-1 analog) conjugation of Gd-containing paramagnetic PSSMA-coated NaGdF4:Yb,Tb,Nd light-upconverting core-shell nanoparticles is developed together with pharmacokinetic and NMR studies attempting various dosage and application modes to mice or rats. Since not only in type 1 diabetes, with autoimmune attack on pancreatic β-cells, but also in progressed type 2 diabetes the β-cell mass is reduced, the information about such reduction is crucial for decision on curing. Currently, there are no established methods how to quantify the β-cell mass in patients. We based our method on excessive presence of the GLP-1 receptors on the β-cell surface and on penetration of nanoparticles to narrow intersticia of pancreatic islets, which cannot be targeted by antibodies. Having simultaneously paramagnetic and light-upconverting nanoparticles enable us to unambiguously identify binding of such nanoparticles to β-cell surface. Preliminary development has been already published (Shapoval a kol., ACS Appl Mater Interfaces 2022 ;14 (16):18233-18247).
The projects is supported by the grant 24-10125S of the Czech Science Foundation (GAČR).
Transplanted islets labeled with PSSMA-coated NaGdF4:Yb,Tb,Nd nanoparticles detected by magnetic resonance imaging. A: control without nanoparticles, B: transplanted islets
Optical imaging of a nanoparticle-labeled islet
