title: Near-infrared fluorescent ribonuclease-A-encapsulated gold nanoclusters: preparation, characterization, cancer targeting and imaging.
abstract: Ultra-small gold nanoclusters (AuNCs) have unique size-dependent optical, electrical and chemical properties. They have emerged as a new nanomaterial with broad applications in optoelectronics, catalysis, biosensing, and bioimaging. Several strategies have been exploited to prepare AuNCs of different "magic number" sizes, using different templates e.g. dendrimers, polyethyleneimines, peptides, and more recently, proteins. Notwithstanding, almost all bio-template-protected AuNCs reported so far exhibit fairly low fluorescence quantum yields (QYs), typically <5%, which is especially true for AuNCs prepared using the protein templates. In this paper, we report a facile, one-pot aqueous synthesis of highly fluorescent AuNCs using bovine pancreatic ribonuclease A (RNase-A) as the bio-template. The as-prepared AuNCs not only fluoresce strongly at the near-infrared (NIR) region (λ(em) = 682 nm), but also exhibit an elevated QY of ∼12%. Additionally, the RNase-A-encapsulated AuNC (RNase-A-AuNC) displays an exceptionally large Stokes shift of ∼210 nm as well as a single dominant fluorescence lifetime of ∼1.5 μs, about three orders of magnitude longer than biological autofluorescence. Furthermore, by coupling vitamin B(12) (VB(12)) to the RNase-A-AuNC, we develop a multifunctional nanoplatform that is suitable for simultaneous targeting and imaging of cancer at the cellular level using Caco-2 cell lines as an in vitro model. Since VB(12) has effective uptake pathways in the digestive system, this nanoplatform may have potential for targeted oral drug delivery in vivo.
authors.affiliation: School of Chemistry and The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. yifeikong@gmail.com
authors.forename: Yifei
authors.initials: Y
authors.lastname: Kong
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Rik
authors.initials: R
authors.lastname: Brydson
authors.forename: Benjamin
authors.initials: B
authors.lastname: Johnson
authors.forename: George
authors.initials: G
authors.lastname: Heath
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Dejian
authors.initials: D
authors.lastname: Zhou
mesh_terms: D018938:Caco-2 Cells; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D008856:Microscopy, Fluorescence / Q000379:methods*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000493:pharmacokinetics*
chemical_list: D020099:Coated Materials, Biocompatible; D006046:Gold; D012259:Ribonuclease, Pancreatic