Chitosan-based multimodal polymeric nanoparticles targeting pancreatic β-cells
Multimodal in vivo imaging of pancreatic islets might improve monitoring of endocrine grafts upon implantation, helping clinical validation of new regenerative therapies based on the replacement of β-cells in type 1 diabetes affected patients. Herein, the generation of chitosan-based multimodal diagnostic nanoparticles (NPs) able to target β-cells is described. The NPs, composed of chitosan (CH) and γ-poly-glutamic-acid (γ-PGA) with different “clickable” functional groups were chemoselectively decorated at the surface with Exendin-4 (Ex4), a ligand of glucagon-like peptide 1 (GLP-1) β-cell receptors, and with a DOTA containing linker, to chelate diagnostic radioisotopes. Furthermore, the NPs were conjugated with IRDye®800CW for multispectral optoacoustic tomography (MSOT). The affinity of Ex4 decorated NPs towards GLP-1R was confirmed by competitive flow cytometry tests. The detectability of the NPs labeled with IRDye®800CW and Ex4 in MSOT experiments was demonstrated. In vivo biodistribution of Ex4 decorated NPs labelled with Ga-68 was studied with positron emission tomography (PET) experiments in mice. Specific binding to GLP-1 receptor expressing tissue was demonstrated in autoradiography experiments, showing potential of the multimodal NPs for specifically targeting β-cells. Multimodal nanoparticles interacting with GLP-1R of β-cells.
Authors
- Felix Lindheimer (ORCID: https://orcid.org/0009-0002-6904-2623)
- Jochen Seißler (ORCID: https://orcid.org/0000-0002-7404-2364)
- Laura Russo (ORCID: https://orcid.org/0000-0002-5914-766X)
- Francesco Nicotra (ORCID: https://orcid.org/0000-0003-1008-196X)
- Eszter Prépost
- Francesca Cadamuro (ORCID: https://orcid.org/0000-0003-2361-6775)
- Magdolna Bodnár
- Zoltán Körhegyi
- Krisztina Kerekes (ORCID: https://orcid.org/0000-0002-6541-8980)
- Magdalena Lindner
- Cataldo Pignatelli (ORCID: https://orcid.org/0000-0002-4231-0504)
- Yi Qiu (ORCID: https://orcid.org/0000-0003-1961-9631)
- András Dinnyés (ORCID: https://orcid.org/0000-0003-3791-2583)
- Judit Kovács‐Kocsi
- Lorenzo Rossi (ORCID: https://orcid.org/0000-0001-7039-8593)
- Sibylle Ziegler (ORCID: https://orcid.org/0000-0002-5321-4817)
- Peter Bartenstein
- Erika Fazekas
Institutions
- Vita-Salute San Raffaele University (IT)
- LMU Klinikum (DE)
- Medizinische Hochschule Hannover (DE)
- Azienda Ospedaliera San Gerardo (IT)
- BioTalentum (Hungary) (HU)
- iThera Medical (Germany) (DE)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Institute of Animal Physiology of the Slovak Academy of Sciences (SK)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
- University of Milano-Bicocca (IT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Carbohydrate Polymer Technologies and Applications
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1016/j.carpta.2024.100610
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.57
Funders
- Horizon 2020
- H2020 Excellent Science