Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages

Abstract

Probiotic Gluconacetobacter strains are intestinal microbes with beneficial effects on human health. Recently, researchers have used these strains to biosynthesize metal and non-metal nanoparticles for treating various chronic diseases. Despite their importance in nanotechnology, gold nanoparticles (AuNPs) biosynthesized by Gluconacetobacter species have not been clearly identified for treating inflammation and inflammation-associated diseases. While ginsenoside CK has strong pharmaceutical activity, it also has strong cytotoxicity and hydrophobicity which is hurdle to make formulation. Peptide-nanoparticle hybrids are gaining increasing attention for their potential biomedical applications, including human inflammatory diseases. Herein, we developed peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3), which intracellularly synthesised by the probiotic Gluconacetobacter liquefaciens kh-1, to target lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The synthetic GNP-CK-CopA3 was characterised by various instrumental techniques. The results of our cellular uptake and MTT assays exhibited obvious drug intracellular delivery without significant cytotoxicity. In addition, pre-treatment with GNP-CK-CopA3 significantly ameliorated LPS-induced nitric oxide (NO) and reactive oxygen species (ROS) production and suppressed the mRNA and protein expression of pro-inflammatory cytokines in macrophages. Furthermore, GNP-CK-CopA3 efficiently inhibited the activation of the nuclear factor-jB (NF-jB) and mitogen-activating protein kinase (MAPK) signalling pathways. Taken together, our findings highlight the potential of using peptide-nanoparticle hybrids in the development of anti-inflammatory approaches and providing the experimental foundation for further application.

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

“…Interestingly, in a recent study, GNPs were made intracellularly using Gluconacetobacter liquefaciens kh-1 (a probiotic strain) and used for synthesizing peptide (CopA3) conjugated nanoparticle (GNP-CK-CopA3) hybrids. Compound K, as peptide-nanoparticle hybrids showed anti-inflammatory effects by inhibiting the activation of NF-kB and MAPK signaling pathways [ 66 ].…”

Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling

“…Applying anti-TNF-α antibodies remarkably suppresses inflammation and increases the survival rate of patients with severe sepsis [ 34 ]. Macrophages also have the ability to produce NO by inducing the expression of iNOS in response to LPS challenge [ 35 ]. iNOS-knockout mice showed decreased mortality in late sepsis, and selective iNOS inhibition alleviated sepsis-induced acute kidney injury [ 36 ].…”

Microbial Fabricated Nanosystems: Applications in Drug Delivery and Targeting

“…Although magnetotactic bacteria and diatoms have drawn privileged focus in terms of designing numerous drug delivery applications, several other microorganisms including bacteria, yeast, fungi, and viruses have also been reportedly used in drug delivery formulations. There are numerous reports of biosynthesis of Gold and silver nanoparticles (El-Sherbiny and Sedki, 2019; Liu et al, 2020). AuNPs are applied due to their unique opto-electronic properties as well as low toxicity; while AgNPs are well-known for their antimicrobial activity.…”

“…Researchers took the services of these biofriendly bacteria to synthesize a hybrid peptide-AuNP loaded with ginsenoside compound K (CK) (GNP-CK-CopA3). The intracellularly placed nanoconjugate was used to specifically target the macrophages and brought considerable reduction in Reactive Oxygen Species (ROS) and pro-inflammatory cytokines at genetic level (Liu et al, 2020) (Figure 4).…”

“…(B) Active targeting of a biosynthesized peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3). The particles, once internalized in macrophages, efficiently suppressed expression of pro-inflammatory cytokines through inhibition of NF-κB and MAPK signaling pathways (Liu et al, 2020). (C) Biosynthesis of HydroxyAPatite (HAP) nanoscaffold inside yeast cell for dual responsive drug delivery against tumor (Ma et al, 2018).…”