Near-infrared fluorescent ribonuclease-A-encapsulated gold nanoclusters: preparation, characterization, cancer targeting and imaging

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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 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 B12 (VB12) 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 VB12 has effective uptake pathways in the digestive system, this nanoplatform may have potential for targeted oral drug delivery in vivo.

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