Gum acacia PEG iron oxide nanocomposite (GA-PEG-IONC) induced pharmacotherapeutic activity on the Las R gene expression of Pseudomonas aeruginosa and HOXB13 expression of prostate cancer (Pc 3) cell line. A green therapeutic approach of molecular mechanism inhibition

Int J Biol Macromol. 2021 Nov 1:190:940-959. doi: 10.1016/j.ijbiomac.2021.08.162. Epub 2021 Aug 31.

Abstract

Among the diverse nanomaterials, polymer-based nanocomposites are gained more attention due to their high efficacy, target biological activities, biodegradability and biocompatibility-gum acacia (GA) - a polymer obtained from acacia trees-is considering the multifunctional nanocomposite synthesis. Distinctive Physico-chemical and biocompatibility properties of gum acacia are utilised to prepare a highly stable, biologically active, eco-friendly Nanocomposite. In this current investigation, gum acacia - poly ethylene glycol grafted iron oxide nanocomposite (GA-PEG-IONC) was synthesised by in situ green science principles. The synthesised Nanocomposite was evaluated against the molecular mechanism of urinary tract pathogenic bacterial strains and prostate cancer cells (Pc 3). Nanocomposite prepared in this examination exhibited notable structural, functional stability with nanoarchitecture which was affirmed by Fourier transform infrared spectroscopy (FTIR), electron microscopic studies, atomic force microscopy (AFM), vibrating sample magnetometric analysis (VSM) and X-ray diffraction (XRD), Synthesised Nanocomposite brought about notable antibacterial activity against urinary tract pathogenic strains by recording potential inhibitory effect on the expression of Las R gene. Inhibition of Las R gene expression reduced notable effect on biofilm development. Anticancer activity against prostate cancer cells (Pc3) was investigated by measurement of HOXB13 gene expression level. Inhibition of HOXB13 gene expression by the IONC brought about structural, functional changes. HOXB13 gene expression inhibition reveals a remarkable cytotoxic effect by recording decreased cell viability. Morphometric analysis by phase-contrast and DAPI fluorescence staining demonstrates that the Nanocomposite prompted cell morphology anomalies or apoptotic changes. Nanocomposite treatment brought about a good sign of Apoptosis by recording enhanced caspase 3 and 9 activities, DNA fragmentation and elevated reactive oxygen species generation (ROS). Hemocompatibility studies were carried out to determine the biocompatibility of the Nanocomposite. Spectrophotometric estimation of plasma haemoglobin, microscopic examination of whole blood cells shows the Nanocomposite was not inciting any indication of toxicity. These findings infer that IONC synthesised in the present study is the promising contender for a broad scope of biomedical applications, especially as an antibacterial and anticancer agent.

Keywords: Anticancer; Biofilm; Gum acacia; HOXB13; Las R; Nanocomposite; Prostate cancer; Pseudomonas aeruginosa; iron oxide.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biofilms / drug effects
  • Caspase 3 / metabolism
  • Catheters
  • DNA Fragmentation / drug effects
  • Escherichia coli / drug effects
  • Ferric Compounds / chemistry*
  • Gene Expression Regulation, Bacterial / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, vpr*
  • Green Chemistry Technology
  • Gum Arabic / chemistry*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Nanocomposites / chemistry*
  • Nanocomposites / ultrastructure
  • PC-3 Cells
  • Phylogeny
  • Polyethylene Glycols / chemistry*
  • Prostatic Neoplasms / genetics*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / genetics*
  • Reactive Oxygen Species / metabolism
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Ferric Compounds
  • HOXB13 protein, human
  • Homeodomain Proteins
  • Reactive Oxygen Species
  • ferric oxide
  • Polyethylene Glycols
  • Gum Arabic
  • Caspase 3