title: Chimeric ferritin nanocages for multiple function loading and multimodal imaging.
abstract: Nanomaterials provide large surface areas, relativeto their volumes, on which to load functions. One challenge, however, has been to achieve precise control in loading multiple functionalities. Traditional bioconjugation techniques, which randomly target the surface functional groups of nanomaterials, have been found increasingly inadequate for such control, which is a drawback that may substantially slow down or prohibit the translational efforts. In the current study, we evaluated ferritin nanocages as candidate nanoplatforms for multifunctional loading. Ferritin nanocages can be either genetically or chemically modified to impart functionalities to their surfaces, and metal cations can be encapsulated in their interiors by association with metal binding sites. Moreover, different types of ferritin nanocages can be disassembled under acidic condition and reassembled at pH of 7.4, providing a facile way to achieve function hybridization. We were able to use combinations of these unique properties to produce a number of multifunctional ferritin nanostructures with precise control of their composition. We then studied these nanoparticles, both in vitro and in vivo, to evaluate their potential suitability as multimodality imaging probes. A good tumor targeting profile was observed, which was attributable to both the enhanced permeability and retention (EPR) effect and biovector mediated targeting. This, in combination with the generalizability of the function loading techniques, promises ferritin particles as a powerful nanoplatfom in the era of nanomedicine.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Quan
authors.forename: Maria A
authors.initials: MA
authors.lastname: Aronova
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Leapman
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000473:pathology*; D013382:Subtraction Technique
chemical_list: D053769:Nanocapsules; D005293:Ferritins