Research Highlights I The use of nanotechnology for drug delivery applications is changing the landscape of pharmaceutical and biotechnology industries by enabling to achieve: i. targeted drug delivery ii. transcytosis of drugs across biological barriers iii. delivery of drugs to intracellular targets iv. visualization of sites of drug delivery (theranostics). To reach such challenging goals, it is essential to engineer the shells of the nanoparticles, since the in vivo fate of the nanocarriers (biodistribution, pharmacokinetics and targeting abilities) depends upon their surface physicochemical properties. Metal-organic frameworks (MOFs), one of the latest classes of ordered porous solids attract growing interest in nanomedicine. In particular, nanosized MOFs (nanoMOFs) based on porous iron (III) polycarboxylates emerged as a new class of versatile, biodegradable and non toxic drug nanocarriers13, 14 NanoMOFs were able to load unprecedented amounts (20-70 wt %) of a variety of drugs able to penetrate within their porous structures.
Whereas there is a plethora of examples of surface engineered dense nanoparticles loaded with drugs, it is extremely challenging to achieve stable, versatile coatings on highly porous nanoparticles without blocking the pores, which in turn alters their ability to adsorb molecules of interest. Three teams in Cyclon Hit closely collaborated to synthesize engineered cyclodextrins able to specifically functionalize the outer surface of porous nanoparticles in a rapid, biofriendly and non-covalent manner. Stable and versatile coatings were obtained within a few minutes by simply incubating, in water, the drug-loaded nanoparticles with the water-soluble cyclodextrin derivatives15. Furthermore, ligands such as mannose were covalently linked to the cyclodextrins, enabling to increase the particle interaction with specific receptors. These results pave the way towards the design of surface-engineered nanoMOFs of interest for applications in the field of targeted drug delivery. Work is in progress to build a library of cyclodextrin derivatives for surface modification.
Water
Cyclodextrin
Drug-loaded nanoparticle
13. P. Horcajada et al. Porous metal–organic-framework
15. V. Agostoni et al. A ‘‘green’’ strategy to construct
nanoscale carriers as a potential platform for drug
non-covalent, stable & bioactive coatings on porous MOF
delivery& imaging. Nat. Mater. 2010, 9, 172.
nanoparticles, Scientific Reports, 2015,
14. P. Horcajada et al. Metal-organic frameworks in biomedicine. Chem. Rev. 2012, 112, 1232.
DOI: 10.1038/srep07925 (open access).