A novel class of 1H-MRI Contrast Agents based on the relaxation enhancement induced on water protons by 14N imidazole moieties

Acknowledgements: This project has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”) and from the ATTRACT project funded by the EC under Grant Agreement No.777222. This work was performed in the frame of the COST Action AC15209 (EURELAX). The Italian Ministry for Educationand Research (MIUR) is gratefully acknowledged for yearly FOE funding to the Euro-BioImaging Multi-Modal Molecular Imaging Italian Node (MMMI).Peer reviewedPostprin

LDL mediated delivery of Paclitaxel and MRI imaging probes for personalized medicine applications

BACKGROUND: The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by flow cytometry analysis. RESULTS: PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 °C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel kabi (PTX Kabi) used in clinical applications. Tumour cells uptake was initially assessed by ICP-MS and MRI on B16-F10 cell line. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. CONCLUSIONS: LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents. For the first time the anon invasive “in vivo” determination of the amount of PTX accumulated in the tumour was possible, thanks to the use of theranostic agents of natural origin. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00955-9