Fluorinated Lipid Nanoparticles for Gene Delivery and Diagnostics

The formulation of drug nanocarriers has attracted increasing attention over the last decades. In particular, the possibility to combine

therapeutic and imaging functionalities in a single nanoplatform (theranostic) has been widely explored to advance therapeutic

approaches and promote the transition from conventional medicine to personalized medicine.

Drug nanocarriers, holding the potential to produce a revolution in medicine, are lipid nanoparticles (LNPs) for gene delivery. They

have proven versatility and efficacy even though today it is still not possible to predict and control their cellular uptake and targeted

delivery. One of the main unmet challenges of LNP formulations is increasing their cellular uptake and gene release into the cytosol.

Currently, it is possible to follow the fate of LNPs after administration only with the addition of labels (e.g., fluorophore) or specific

ribonucleic acid (RNA) sequence encoding for fluorescent protein. This results in the lack of possibility to follow the fate of LNPs once

administered in vivo with a non-invasive imaging technique. Theranostic strategies to deliver RNA and simultaneous imaging of

target organs is an important unmet goal.

Recently, it has been demonstrated that fluorination of components in gene delivery vehicles strongly improved their cellular uptake

and, most importantly, their gene endosomal escape. The fluorination strategies investigated so far use either -CF3 groups or long

linear perfluoroalkyl chains, but a tailored design of the fluorinated group could also endow the nanocarrier with excellent imaging

functions. In this context, FluoNeeD strategy is to tailor fluorination of LNPs in order to: (i) improve their therapeutic efficacy by

enhancing LNP cellular uptake and promoting gene endosomal escape; (ii) render LNPs trackable in vivo by 19F-MRI and in vitro/ex vivo by Raman microscopy.