Cell-Penetrating Peptide Conjugated Au Nanoclusters Selectively Suppress Refractory Lymphoma Cells via Targeting Both Canonical and Noncanonical NF-κB Signaling Pathways

Abstract

Activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is the most aggressive form of DLBCL, with a significantly inferior prognosis due to resistance to the standard R-CHOP immunochemotherapy. Survival of ABC-DLBCL cells addicted to the constitutive activations of both canonical and noncanonical NF-κB signaling makes them attractive therapeutic targets. However, a pharmaceutical approach simultaneously targeting the canonical and noncanonical NF-κB pathway in the ABC-DLBCL cell is still lacking. Peptide-conjugated gold nanoclusters (AuNCs) have emerged unique intrinsic biomedical activities and possess a great potential in cancer theranostics. Here, we demonstrated a Au 25 nanocluster conjugated by cell-penetrating peptides that can selectively repress the growth of ABC-DLBCL cells by inducing efficient apoptosis, more efficiently than glutathione (GSH)-conjugated AuNCs. The mechanism study showed that the cell-penetrating peptides enhanced the cellular internalization efficiency of AuNCs, and the selective repression in ABC-DLBCL cells is due to the inhibition of inherent constitutive canonical and noncanonical NF-κB activities by AuNCs. Several NF-κB target genes involved in chemotherapy resistance in ABC-DLBCL cells, including anti-apoptotic Bcl-2 family members and DNA damage repair proteins, were effectively down-regulated by the AuNC. The emerged novel activity of AuNCs in targeting both arms of NF-κB signaling in ABC-DLBCL cells may provide a promising candidate and a new insight into the rational design of peptide-conjugated Au nanomedicine for molecular targeting treatment of refractory lymphomas.

Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis via Nrf2-Dependent Macrophage Reprogramming

“…In this study, we first synthesized a peptide-templated gold nanocluster with γ-GSH (designated GA, Au 29 SG 27 ) according to our previously published method. , GSH is an endogenous thiol-tripeptide and expressed across the human colon mucosa . We speculated GSH-conjugated gold nanoclusters could be well tolerated by colonic cells and therefore exert the immunoregulatory effect of Au more efficiently.…”

Different Targeting Ligands-Mediated Drug Delivery Systems for Tumor Therapy

“…This sub-section reviews two main peptidetargeted drug delivery systems for cancer therapy applications: peptide-drug conjugates and peptide-conjugated nanoparticles [50,51]. Sv peptide Gold Nanoclusters Refractory lymphomas [63] Abbreviations are as follows: (TTP): tumor targeting peptide, and (CPP): cell penetrating peptide.…”

The roles of templates consisting of amino acids in the synthesis and application of gold nanoclusters

“…200 Red-emitting P–AuNCs with cell-penetrating peptide (CCYGGPKKKRKVG) can selectively repress the growth of activated B cell-like diffuse large B-cell lymphoma (ABC–DLBCL) cells due to the inhibition of inherent constitutive canonical and noncanonical NF-κB activities with the increase in the cellular internalization efficiency of AuNCs. 201 Nine highly positively charged tridecapeptides (CCYGGPKKKRKVG) were used as ligands to form AuNCs with favorable solubility. The P–AuNCs easily penetrated the membrane, and effectively bound and inhibited thioredoxin reductase 1 (TrxR1), leading to tumor cell apoptosis.…”