Doubly derivatized poly(lactide)–albumin nanoparticles as blood vessel-targeted transport device for magnetic resonance imaging (MRI)

• Published in: Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology Vol. 23; no. 2
• Main Authors: Pashkunova-Martic, Irena, Kremser, Christian, Talasz, Heribert, Mistlberger, Klaudia, Bechter-Hugl, Beate, Pfaller, Kristian, Baurecht, Dieter, Debbage, Paul, Jaschke, Werner, Helbich, Thomas H., Keppler, Bernhard
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2021; Springer Nature B.V
• Subjects: Antibodies; Binding; Biodegradability; Biodegradation; Blood vessels; Bovine serum albumin; Characterization and Evaluation of Materials; Chemistry and Materials Science; Contrast agents; Contrast media; Core-shell structure; Coupling; Coupling (molecular); Crosslinking; Electron microscopy; Endothelial cells; Endothelium; Gadolinium; Inorganic Chemistry; Lasers; Lectins; Lipophilic; Macromolecules; Magnetic resonance imaging; Materials Science; Medical imaging; Microscopy; Nanoparticles; Nanotechnology; Optical Devices; Optics; Photonics; Physical Chemistry; Polylactic acid; Reagents; Research Paper; Serum albumin; Size exclusion chromatography; Tomatoes; Transmission electron microscopy; Veins; Nanoparticles; Poly(lactide)-albumin; Tomato lectin; Targeting; MRI; Endothelial cells
• ISSN: 1388-0764; 1572-896X
• DOI: 10.1007/s11051-021-05157-w

Molecular imaging using magnetic resonance imaging (MRI) is expected to play a crucial future role in oncological diagnosis and in monitoring of therapeutic progress. Targeted nanoparticle contrast media (CM) with high relaxivities are required in order to obtain adequate signal-to-noise ratios as well as visualization of a desired pathologic area of the human body. The aims of this study were to synthesize and define certain physicochemical and enhancement properties of new doubly derivatized polylactic acid–bovine serum albumin (PLA-BSA) nanoparticles (NPs) modified by the covalent coupling of glutaraldehyde as a crosslinking agent. An additional functionalization with endothelial cells (ECs) targeting groups (tomato lectins; LEA) and signal-emitting moieties (DTPA-Gd) enables its use as a macromolecular, biodegradable contrast agent for MRI. The NPs were characterized by different spectroscopies, size exclusion chromatography, and scanning and transmission electron microscopy. In a human vein model, the dynamics of the nanoparticle interactions with the vein wall were examined in MRI, with correlative imaging in electron microscopy. In vitro studies were conducted to show endothelial binding and persistent enhancement at the apical EC surface. NPs with a diameter between 55 and 75 nm, able to carry simultaneous signal emitting, and targeting motifs on a single construct were successfully prepared. A high Gd payload and endothelial binding to blood vessel walls were observed. The binding affinity and specificity of LEA was preserved, and a strong enhancement at the endothelium was achieved. The stabilized core–shell structure of PLA-NP might allow for further encapsulation of lipophilic drugs or for attachment of other targeting molecules, such as antibodies. Graphical abstract