Application of zirconium MOFs in drug delivery and biomedicine

Isabel Abánades Lázaro, Ross S. Forgan
2019 Coordination chemistry reviews  
Nanoparticulate metal-organic frameworks (MOFs) have the requisite high storage capacities, tailorable structures, ease of functionalisation, and excellent biocompatibilities for application as nanoscale drug delivery devices (DDSs). Zirconium MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and so are particularly suited for biological applications. This review covers the use of Zr MOFs as DDSs with focus on the different
more » ... properties that makes them attractive for use. The various methods for modifying the surfaces of Zr MOFs are described with pertinent examples of the resulting enhancements in aqueous stability, colloidal dispersion, and stimuli-responsive drug release. The in vitro and in vivo application of Zr MOFs for photodynamic therapy and drug delivery are discussed with respect to the structural features of the MOFs and their surface functionality, and perspectives on their future applications and analogous hafnium MOFs are given. Keywords: metal-organic frameworks; drug delivery; zirconium; biomedicine; in vivo; in vitro; imaging The organic/inorganic nature of MOFs has positioned them as an attractive alternative to the drawbacks that nanomedicine is currently facing, as it offers almost unlimited possibilities to design desired structures through metal-linker chemistry and postsynthetic modification in order to enhance their drug delivery properties, such as high drug loadings, controllable release of the drug, low cytotoxicity, appropriate colloidal stability and degradation rates, efficient cell internalisation, and anticancer cell selectivity [23] [24] [25] . As well as drug delivery, significant efforts have been made to interface MOFs with biological entities [26, 27], for example encapsulating enzymes for catalysis [28], viruses for room temperature vaccines [29], and even living cells [30] within MOF scaffolds. Since Ferey and co-workers reported the first study of iron-based MOFs for applications in biomedicine [31], a tremendous amount of work has emerged towards developing the great potential for various applications of nanoparticulate MOFs (NMOFs) in healthcare [16, 32-36] Iron MOFs are probably the most widely studied materials for healthcare applications to date, because iron is well tolerated, with a 50% lethal dose (LD 50 ) of 30 gkg -1 when orally administered to rats, while their high porosity enables very high drug loadings [31, [37] [38] [39] [40] [41] . Interest in zirconium-based MOFs [42] for biomedical applications has increased of late as zirconium is also a biocompatible metal: the human body typically contains about 300 mg of zirconium, and the recommended daily ingestion is 4.15 mg per day [43] . The LD 50 of zirconyl acetate in rats, as determined by in vivo experiments, has been found to be 4.1 gkg -1 , which is lower but still comparable to iron [44] . Additionally, the hard Lewis acid/base coordination nature of the Zr-carboxylate bonds can render them more chemically and mechanically stable than iron MOFs and other high valent materials [45] [46] [47] , facilitating postsynthetic functionalisation without compromising materials properties [48] maintaining excellent porosity and molecular storage capacities [49] and ultimately resulting in higher physiological stability [50]. In this review, we describe the various efforts to develop Zr MOFs as DDSs, and in biomedicine in general. The differing structures and functionalisation protocols for Zr MOFs are highlighted, in particular focussing on external surface modification and the subsequent effects on properties such as stability and dispersion. In vitro and in vivo applications of Zr MOFs are described in the context of structure-property relationships, and future research directions are discussed.
doi:10.1016/j.ccr.2018.09.009 fatcat:vqdquybppbgfpfvixm6ddlc7ie