Engineering of magnetic-based nanoplatforms for theranostic

FREIS, BARBARA; RAMIREZ, MARIA DE LOS ANGELES; TASSO, MARIANA; BÉGIN, SYLVIE

Workshop; Fronteras en Nanobiotecnología III; 2022

In nanomedicine, the goal is to develop multimodal nanoparticles (NPs) to speed up targeted diagnosis, to increase its sensitivity, reliability and specificity for a better management of the disease (patient’s care) and to treat the disease in a specific personalized manner in feedback mode. Combination of therapies to target individual cancer-specific vulnerabilities is a way to increase the efficacy of anticancer treatment. Therefore, besides precision diagnosis, challenges for personalized nanomedicine are to develop multifunctional thera-nostic nanoplatforms to be able to target specifically tumoral cells, to test quickly different treatments and to follow-up the effect(s) of the treatments by imaging. The selective accumulation of NPs in diseased organs to enable precise diagnosis and targeted therapy remains also an important issue. Most of developed NPs accumulate, after intravenous injection, in eliminatory organs and only low amounts are seen accumulating intumours. For a precise treatment, active targeting with affinity ligands to achieve tumor specificity is crucial.Among NPs developed for nanomedicine, superparamagnetic iron oxide nanoparticles (IONPs) are promising as they may be designed to display multimodal therapy. Indeed, besides being excellent T2 contrast agents for MRI, IONPs are promising as therapeutic agents by magnetic hyperthermia when correctly designed. To be a good heating agent, IONPs have to display a high magneto-cristalline anisotropy and ways to increase itare to tune the NPs size and shape. IONPs have also an interest for photothermal treatment as they express a good photothermal response to laser irradiation.In that context, we have developed IONPs coated with an original dendron molecule (DNPs) which have been demonstrated in several in vitro and in vivo studies to display antifouling properties (no strong RES accumulation). With their favourable biodistribution and bioelimination profile, dendronized NPs (DNPs) are very well adapted for investigating affinity targeting. First targeting experiments have demonstrated that, after intravenous injection in melanoma mice model, DNPs coupled with a melanin targeting ligand were specifically uptaken by melanoma tumor cells with very favorable biodistribution and biokinetic properties. Recently, we have studied the targeting of head and neck cancer cells by coupling selected targeting ligands on DNPs’surface and demonstrated the strong specificity of GE11-like peptide for internalizing high amount of DNPs.The coupling method of targeting ligands and their grafting yield were important issues to face.Then, IONPs with different sizes and shapes have been designed by using the thermal decomposition synthesis method to evaluate their potential to combine different therapeutic modes. We have tuned different synthesis parameters and IONPs with different shapes were thus synthesized and dendronized. The effect of the NPs size and shape on magnetic hyperthermia and photothermia has been investigated allowing to establish the optimal NPs design to combine therapies.The rational design of IONPs as contrast agents for MRI and heating agent and the implementation of targeting strategies are of key importance to face the actual needs on the development of better performing nanoplatforms for nanomedecine.Such smart approach, when translated to clinical uses, would have a great impact on the cancer management to improve patient survival and quality of life.