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Self Immolative Nanoparticles

Self-immolation is a new and extremely promising approach to drug delivery recently developed and not yet deeply explored.

Self immolative (SI) structure are smart materials that undergo spontaneous and rapid disassembling following a specific triggering event[1], for instance an enzymatic cleavage[2], irradiation[3], pH variation[4], etc., leading to the formation of the constituent basic units of the macrostructure and the release of the linked drug (Figure 1). As such, when a pharmaceutical compounds or probes are linked to the SI system, their release can be controlled by just modifying the chemical design of the material.

While most of the literature and current studies are focused on the development either of SI polymers or dendrimers, this project aims to the production of SI cross-linked polymeric nanoparticles (NP) in order to combine two of the most promising strategies in drug delivery, self-immolation and nanotechnology, that can address one the limitations of the other. Our research work widen from the synthesis of the basic units (functionalised carbamates), to their polymerization and nanoparticles formation, until the in vitro and in vivo (using zebrafish models, link to project n.6) toxicological evaluation of the nanoparticles to be used as new drug delivery systems (DDS), covering all the physico-chemical and biological studies required in order to develop a new pharmaceutical system.

Figure 1
Figure 4: Scheme of self-immolative cross-linked polymeric nanoparticles

References
1. G. I. Peterson, M. B. Larsen; A. J. Boydston, Macromolecules, 2012, 45, 7317-7328.
2. L. Stern, R. Perry, P. Ofek, A. Many, D. Shabat; R. Satchi-Fainaro, Bioconjugate Chem., 2009, 20, 500510.
3. M. Fomina, C. L. McFearin; A. Almutairi, Chem. Commun., 2012, 48, 91389140.
4. A. P. Esser-Kahn, N. R. Sottos, S. R. White; J. S. Moore, J. Am. Chem. Soc., 2010, 132, 1026610268.


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