New publication in ACS Applied Materials and Interfaces entitled “Hybrid metal-phenol nanoparticles with polydopamine-like coating for PET/SPECT/CT imaging” with Dr. Salvio Suárez-García as the first author and in collaboration with the group of Prof. Urs Häfeli from the University of British Columbia (UBC, Vancouver, Canada).
In this work, the authors present a simple one-step assembly method to synthesize metal-phenolic nanoparticles (MPNs) by mixing In(III) with the imidazole, 1,4-bis(imidazole-1-ylmethyl)-benzene, and the catechol, 3,4-dihydroxycinnamic acid, as co-ligands. The surface was then functionalized with a polydopamine-like coating by crosslinking pyrocatechol with hexamethylenediamine under oxidizing conditions, a one-step method for the functional modification of nanomaterials, followed by PEGylation and functionalization with folic acid (FA). A radioactive version of these MPNs was prepared chelator-free by mixing in 111In(III) during the initial synthesis. With a relatively long half-life of 2.807 days, the 111In-labeled MPNs were used for in vitro assessments, such as stability and cell uptake studies, and for preclinical single-photon emission computed tomography (SPECT/CT) imaging. To assess whether the addition of FA moieties targeted the MPNs in vivo, the distribution of radiolabeled In-MPN-FA was compared to In-MPN-PEG in mice bearing CT26 tumors that overexpress FA-receptors. Finally, the ability of the synthesized MPNs to simultaneously incorporate metal ions, motivated the authors to further radiolabel homologous Cu-MPN-PEG NPs with 64Cu(II) and to evaluate the resulting MPN’s suitability for diagnostic positron-emission tomography (PET) imaging.
ABSTRACT: The validation of metal–phenolic nanoparticles (MPNs) in preclinical imaging studies represents a growing field of interest due to their versatility in forming predesigned structures with unique properties. Before MPNs can be used in medicine, their pharmacokinetics must be optimized so that accumulation in nontargeted organs is prevented and toxicity is minimized. Here, we report the fabrication of MPNs made of a coordination polymer core that combines In(III), Cu(II), and a mixture of the imidazole 1,4-bis(imidazole-1-ylmethyl)-benzene and the catechol 3,4-dihydroxycinnamic acid ligands. Furthermore, a phenolic-based coating was used as an anchoring platform to attach poly(ethylene glycol) (PEG). The resulting MPNs, with effective hydrodynamic diameters of around 120 nm, could be further derivatized with surface-embedded molecules, such as folic acid, to facilitate in vivo targeting and multifunctionality. The prepared MPNs were evaluated for in vitro plasma stability, cytotoxicity, and cell internalization and found to be biocompatible under physiological conditions. First, biomedical evaluations were then performed by intrinsically incorporating trace amounts of the radioactive metals 111In or 64Cu during the MPN synthesis directly into their polymeric matrix. The resulting particles, which had identical physicochemical properties to their nonradioactive counterparts, were used to perform in vivo single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in tumor-bearing mice. The ability to incorporate multiple metals and radiometals into MPNs illustrates the diverse range of functional nanoparticles that can be prepared with this approach and broadens the scope of these nanoconstructs as multimodal preclinical imaging agents.