N‐Heterocyclic Carbene–Gold(I) Complexes Conjugated to a Leukemia‐Specific DNA Aptamer for Targeted Drug Delivery

Abstract

This report describes the synthesis and characterization of novel N-heterocyclic carbene (NHC) gold(I) complexes and their bioconjugation to the CCRF-CEM leukemia specific aptamer sgc8c. Confirmation of successful bioconjugation was achieved by using fluorescent tags on both the NHC-Au(I) complex and the aptamer. Cell viability assays indicate the NHC-Au(I)-aptamer conjugate is more cytotoxic than the NHC-gold complex alone. A combination of flow cytometry, confocal microscopy, and cell viability assays provide clear evidence that the NHC-Au(I)-aptamer conjugate is selective for targeted CCRF-CEM leukemia cells.

A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect

“…This potentiates aptamers to be produced in large scale with controllable batch-to-batch variations and be customized and modified for specific purposes. 11 , 12 , 13 , 14 , 15 , 16 , 17 Over the past years, aptamers have been shown to serve as successful guiding molecules for targeted delivery, with good tissue penetration efficiency. 13 , 18 , 19 , 20 Recent aptamer-related research has further extended the field into functional aptamer therapeutics, especially in the field of immuno-oncology, an area full of new hope and uncertainty.…”

(C^Npz^C)AuIII complexes of acyclic carbene ligands: synthesis and anticancer properties

“…12 Gold(I/III) complexes have also been shown to stabilize the G-quadruplex structure of DNA. 13 Post-metallation modifications have appeared as a very efficient and high-yielding method of introducing elaborated scaffolds into metal complexes, for example for derivatising metal gold complexes with peptides, 14 aptamers 15 or other metal complexes. 16 The first gold(III) acyclic carbenes were reported in the 1970s by Balch et al and…”

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

“…DOX was released into the CEM (human leukemia) cell nucleus when exposed to the low‐pH of the lysosomes (Figure 13b). Veige and co‐workers conjugated a N‐heterocyclic carbene (NHC) to gold to form carbene–gold(I) complexes functionalized with CCRF‐CEM‐leukemia‐selective aptamers for targeted drug delivery to leukemia cancerous CEM cells monitored by fluorescence …”

“…Unfortunately, this strategy is prone to enzymatic degradation in the blood circulation . Aptamers were also conjugated to functional materials by an amide linker or sulfonamide linker . However, complementary base pairing for conjugating aptamers to materials was shown as an effective alternative strategy for in vivo applications with appropriate stability .…”

“…[142] Veige and co-workers conjugated a N-heterocyclic carbene (NHC) to gold to form carbene-gold(I) complexes functionalized with CCRF-CEM-leukemia-selective aptamers for targeted drug delivery to leukemia cancerous CEM cells monitored by fluorescence. [143] AuNPs have been reported that were functonalized with the MUC-1 aptamer, which targets the mucin 1 (MUC-1) receptor. [144,145] Among the reported AuNPs, an imaging agent with an additional silica shell was used to target human breast cancer MDA-MB-468 cells with MUC-1 expression ( Figure 13c).…”