TRAIL/S-layer/graphene quantum dot nanohybrid enhanced stability and anticancer activity of TRAIL on colon cancer cells

Abstract

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), known as a cytokine of the TNF superfamily, is considered a promising antitumor agent due to its ability to selectively induce apoptosis in a wide variety of cancer cells. However, failure of its successful translation into clinic has led to development of nano-based platforms aiming to improve TRAIL therapeutic efficacy. In this regard, we fabricated a novel TRAIL-S-layer fusion protein (S-TRAIL) conjugated with graphene quantum dots (GQDs) to benefit both the self-assembly of S-layer proteins, which leads to elevated TRAIL functional stability, and unique optical properties of GQDs. Noncovalent conjugation of biocompatible GQDs and soluble fusion protein was verified via UV–visible and fluorescence spectroscopy, size and ζ-potential measurements and transmission electron microscopy. The potential anticancer efficacy of the nanohybrid system on intrinsically resistant cells to TRAIL (HT-29 human colon carcinoma cells) was investigated by MTT assay and flow cytometry, which indicated about 80% apoptosis in cancer cells. These results highlight the potential of TRAIL as a therapeutic protein that can be extensively improved by taking advantage of nanotechnology and introduce S-TRAIL/GQD complex as a promising nanohybrid system in cancer treatment.

The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer

“…The hallmarks of cancer in terms of cellular proliferation, migration, clonogenic potential, evasion of apoptosis, and metastasis threaten the normal cellular homeostasis 41 . Despite improvements in detection, diagnostic and therapeutic avenues, the prognosis of CRC still shows dismal rates 9 . Thus, a comprehensive analysis of signaling cross-talks and molecular players that trigger its initiation and progression is required.…”

“…Accumulation of genetic mutations, aberrant cellular signaling pathways, heightened expression of oncogenes, and suppression of tumor suppressor genes together contribute to the invasive carcinoma condition. Apt and efficient screening programs can significantly reduce the risk through early detection and immediate administration of treatment modalities 9–12 .…”

Recent advances of graphene–biomacromolecule nanocomposites in medical applications

“…The composite structure benefited both the S-layer protein self-assembly and the functional stability of TRAIL. 145 The cytotoxicity of the hybrid system against human colon cancer cell lines was tested by flow cytometry, and the experimental results showed that S-TRAIL/GQDs had high stability and could be used as a promising candidate for cancer therapy.…”

Research Progress of Conjugated Nanomedicine for Cancer Treatment

“…This platinum-single-walled carbon nanotube structure containing folic acid has the targeting ability, which increases the activity of the platinum-based anticancer drug and significantly enhances the cell killing performance [ 142 ]. Recently, quantum dots (QDs) and ceramic-based nanoparticles have been paid more attention to due to their anticancer potential [ 143 , 144 ].…”