Turning On/Off the Anti-Tumor Effect of the Au Cluster via Atomically Controlling Its Molecular Size

Abstract

We reported two Au clusters with precisely controlled molecular size (AuPeptide and AuPeptide) showing different antitumor effects. In vitro, both AuPeptide and AuPeptide were well taken up by human nasopharyngeal cancer cells (CNE1 cells). However, only AuPeptide significantly induced CNE1 cell apoptosis. Further studies showed that CNE1 cells took up AuPeptide (1.98 × 10 mol/cell), and 9% of them entered mitochondria (0.186 × 10 mol/cell). As a comparison, the uptake of AuPeptide was only half the amount of AuPeptide (1.11 × 10 mol/cell), and only 1% of them entered mitochondria (0.016 × 10 mol/cell). That gave 11.6-fold more AuPeptide in mitochondria of CNE1 cells than AuPeptide. Further cell studies revealed that the antitumor effect may be due to the enrichment of AuPeptide in mitochondria. AuPeptide slightly decreased the Mcl-1 (antiapoptotic protein of mitochondria) and significantly increased the Puma (pro-apoptotic protein of mitochondria) expression level in CNE1 cells, which resulted in mitochondrial transmembrane potential change and triggered the caspase 9-caspase 3-PARP pathway to induce CNE1 cell apoptosis. In vivo, CNE1 tumor growth was significantly suppressed by AuPeptide in the xenograft model after 3 weeks of intraperitoneal injection. The TUNEL and immuno-histochemical studies of tumor tissue verified that CNE1 cell apoptosis was mainly via the Puma and Mcl-1 apoptosis pathway in the xenograft model, which matched the aforementioned CNE1 cell studies in vitro. The discovery of Au but not Au suppressing tumor growth via the mitochondria target was a breakthrough in the nanomedical field, as this provided a robust approach to turn on/off the nanoparticles' medical properties via atomically controlling their sizes.

Peptide-Templated Gold Clusters as Enzyme-Like Catalyst Boost Intracellular Oxidative Pressure and Induce Tumor-Specific Cell Apoptosis

“…Next, mass spectrometry expediently provides the precise composition of AuCs, that is, the number of noble metal atom and ligand. In our case, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was used to characterize the accurate formula of AuCs [18,19,20,21,22,23]. As shown in Figure 1d, MS of AuCs has several main peaks between 1550 and 1800 m/z.…”

Biomolecular interactions of ultrasmall metallic nanoparticles and nanoclusters

“…So far, usNPs have been developed as self-therapeutic agents, 325 drug delivery vehicles, 326 radiosensitizers for cancer radiotherapy, 6,327,328 among other applications in cancer nanomedicine. However, despite promising results so far, commonly encountered limitations such as restricted tumor uptake and off-target localization may hamper the clinical applications of usGNPs.…”

Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications

“…Interestingly, Zhai et al. 167 reported two Au clusters with precisely controlled molecular size (Au 5 Peptide 3 and Au 22 Peptide 10 ) showing different antitumor effects. Au 5 , but not Au 22 , suppressed tumor growth by targeting the mitochondria, and this was a breakthrough in the nanomedical field.…”