An important part of nanomedicine research is devoted to the development of multifunctional nanoparticles (NP) for targeted drug delivery or else as imaging tools for both, advanced therapeutic and diagnostic applications.1 However, even if huge progress has been made in the field, many obstacles remain to be addressed toward full utilization of these powerful NP in the clinic and to improve their translational value.2 A more cross-disciplinary and comprehensive vision of this multifaceted research is now recommended, including new considerations in: i) clearance pathways, ii) targeting strategies, iii) personalized/predictive medicine and iv) high-scale GMP production.3,4

After a review of these new considerations through a succinct presentation of previous works, this seminar will focus on the application of novel oligosaccharides (OS) as very promising coatings for the design of NP intended for targeted and personalized therapy in oncology. We will show in what way OS preparation by depolymerisation of their native polysaccharide parents, already widely used in nanomedicine, could overcome the limitations of these natural polymers and open new exciting perspectives. In particular, we will discuss how OS-based functional coatings could answer major criteria for successful development of NP such as: an optimal renal clearance, a targeting enhancement through interactions with tumour microenvironment’s components with resultant therapeutic effect, or simplification of the NP synthesis by achieving a number of simultaneous specific functions.

To illustrate these strategies, we will give details of a pioneer study that use different heparin oligosaccharides (HEP-OS) combined with a new generation of extremely small iron oxide nanoparticles (ESIONP) able to perform positive contrast in magnetic resonance imaging (MRI).5 This study has demonstrated that the HEP-OS length controls the core size during the synthesis and the polymer conformation at the ESIONP’s surface, allowing to achieve optimal MRI contrast. Also, HEP-OS coated ESIONP were endowed directly with a discriminated specific bioactivity according to the HEP-OS used. The most relevant point was the in vivo nuclear imaging-based biodistribution study that revealed drastic changes in the probes behaviours: the shortening of HEP-OS promoting a shift from hepatic to renal clearance. Overall, by fine tuning of the HEP-OS length, we were able to identify a candidate showing prolonged vascular lifetime and accumulation in a tumour xenograft, balanced with a low uptake by non-specific organs and favourable urinary clearance.

You can join the seminar at: https://rediris.zoom.us/j/88389034450?pwd=UzcvdTNXRjQxWTlzM2oycTBQVmNBUT09