Highly Luminescent Folate‐Functionalized Au₂₂ Nanoclusters for Bioimaging

Abstract

Gold nanoclusters are emerging as new materials for biomedical applications because of promises offered by their ultrasmall size and excellent biocompatibility. Here, the synthesis and optical and biological characterizations of a highly luminescent folate-functionalized Au cluster (Au -FA) are reported. The Au -FA clusters are synthesized by functionalizing the surface of Au (SG) clusters, where SG is glutathione, with benzyl chloroformate and folate. The functionalized clusters are highly water-soluble and exhibit remarkably bright luminescence with a quantum yield of 42%, significantly higher than any other water-soluble gold clusters protected with thiolate ligands. The folate groups conjugated to the gold cluster give rise to additional luminescence enhancement by energy transfer sensitization. The brightness of Au -FA is found to be 4.77 mM cm , nearly 8-fold brighter than that of Au (SG) . Further biological characterizations have revealed that the Au -FA clusters are well-suited for bioimaging. The Au -FA clusters exhibit excellent photostability and low toxicity; nearly 80% cell viability at 1000 ppm of the cluster. Additionally, the Au -FA clusters show target specificity to folate-receptor positive cells. Finally, the time-course in vivo luminescence images of intravenous-injected mice show that the Au -FA clusters are renal-clearable, leaving only 8% of them remained in the body after 24 h post-injection.

Ultrasmall noble metal nanoparticles: Breakthroughs and biomedical implications

“…The surprising wide-spectrum antimicrobial activity is a size-dependent phenomenon and only occurs to ultrasmall AuNCs. Moreover, UNMNPs of certain sizes often possess photoluminescent characters, such as Au 5 [54], Au 8 [48], Au 22 [70], Au 23 [56], Au 25 [71], Ag 9 [72], Ag 14 [73], Pt 5 [27] and Pt 8 [74] nanoclusters, which can be developed as in vitro [27, 73, 74] and in vivo [70, 75] imaging agents, as well as various optical sensors[71, 72, 76]. More applications of luminescent noble metal nanoclusters in bioimaging and biosensing can be found in other review articles[35, 77–79].…”

“…in the second NIR window 1000–1350nm) are desired. Highly luminescent water-soluble Au 22 nanoclusters with a quantum yield (QY) of 42% were synthesized by Lee et al and applied to in vivo imaging[212]. The unprecedented high QY for NIR-emitting thiolated AuNCs was achieved by simultaneously rigidifying the gold shell of Au 22 via surface conjugation with strong π - π stacking molecules (benzyl chloroformate) and enabling resonance energy transfer from the conjugated ligands (folate) to Au 22 nanoclusters (Fig.…”

Ultra‐small Albumin Templated Gd/Ru Composite Nanodots for In Vivo Dual modal MR/Thermal Imaging Guided Photothermal Therapy

“…Flow cytometry was used to detect the cell's endocytosis of fluoresceine isothiocyanate (FITC) labeled GRBNDs . A time‐dependent cellular uptake phenomenon was observed, which is highly advantageous to generate strong hyperthermia in the cells (Figure h).…”

Molecular reactivity of thiolate-protected noble metal nanoclusters: synthesis, self-assembly, and applications

“…Due to their small size, strong luminescence, good biocompatibility and efficient renal clearance, metal NCs have potential applications in diverse sectors of biomedicine, like bioimaging, 224,225 cancer therapy 226 and antimicrobial activity. 126,227 The most commonly used molecular reaction of metal NCs in these biomedical applications is covalent conjugation reaction that confers additional functional moieties to NCs, including active targeting moieties 122,124,228,229 and therapeutic moieties. 125,126,229 For example, since the overexpression of folate receptors has been observed on the surface of many cancer cells, Pyo et al conjugated folic acid (FA) to Au 22 (SG) 18 NCs through EDC chemistry, which can enhance the luminescence of Au NCs (QY ¼ 42%, $6.5-fold higher than that of the original Au 22 (SG) 18 ) and improve the targeting efficacy toward folate-receptor positive KB and HeLa cells.…”

“…125,126,229 For example, since the overexpression of folate receptors has been observed on the surface of many cancer cells, Pyo et al conjugated folic acid (FA) to Au 22 (SG) 18 NCs through EDC chemistry, which can enhance the luminescence of Au NCs (QY ¼ 42%, $6.5-fold higher than that of the original Au 22 (SG) 18 ) and improve the targeting efficacy toward folate-receptor positive KB and HeLa cells. 122 Similarly, by using EDC chemistry, Chen et al co-conjugated FA and Au 29-43 (SG) 27-37 to a pH-responsive amphiphilic copolymer, poly(DBAM-co-NAS-co-HEMA) or PDNH for short, where DBAM, NAS, and HEMA denote 4-n-dodecyloxybenzalacetal, N-succinimidylmethacrylate, and 2-hydroxyethyl methacrylate, respectively. Aer loading the anti-cancer drug paclitaxel (PTX), the Au NC-PDNH composite can simultaneously provide active targeting ability, luminescent imaging activity, and therapeutic effect in female athymic nude mice bearing HeLa tumors.…”