In vitro and Microbiological Assay of Functionalized Hybrid Nanomaterials To Validate Their Efficacy in Nanotheranostics: A Combined Spectroscopic and Computational Study

ChemMedChem. 2021 Dec 14;16(24):3739-3749. doi: 10.1002/cmdc.202100494. Epub 2021 Oct 8.

Abstract

Functionalized nanoparticles reveal new frontiers in therapeutics and diagnostics, simultaneously referred to as theranostics. Functionalization of an inorganic nanoparticle (NP) with an organic ligand determines the interaction of the functionalized NPs with various cellular components, leading to the desired therapeutic effect, while diminishing adverse side effects. Apart from the therapeutic effect of the nanoparticles, other physical properties of the organic-inorganic complex (nanohybrid) including fluorescence, X-ray or MRI contrast offer diagnosis of the anomalous target cell. In this study we functionalized Mn3 O4 NPs with organic citrate (C-Mn3 O4 ) and folic acid (FA-Mn3 O4 ) ligands and investigated their antimicrobial activities using Staphylococcus hominis as a model bacteria, which can be remediated through their membrane rupture. While high-resolution transmission microscopy (HR-TEM), XRD, DLS, absorbance and fluorescence spectroscopy were used for structural characterisation of the functionalised NPs, zeta potential measurements and temperature-dependent reactive oxygen speices (ROS) generation reveal their drug action. We used high-end density functional theory (DFT) calculations to rationalise the specificity of the drug action of the NPs. Picosecond-resolved FRET studies confirm the enhanced affinity of FA-Mn3 O4 to the bacteria relative to C-Mn3 O4 , leading to enhanced antimicrobial activity. We have shown that the functionalised nanoparticles offer significant X-ray contrast in in-vitro studies, indicating the FA-Mn3 O4 NPs to be a potential theranostic agent against bacterial infection.

Keywords: Mn3O4 NPs; Nano-bio interface; Nanoparticles; Surface functionalization; Theranostics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Citric Acid / chemistry
  • Citric Acid / pharmacology
  • Density Functional Theory*
  • Dose-Response Relationship, Drug
  • Dynamic Light Scattering
  • Folic Acid / chemistry
  • Folic Acid / pharmacology
  • Manganese Compounds / chemistry
  • Manganese Compounds / pharmacology
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Nanoparticles / chemistry
  • Oxides / chemistry
  • Oxides / pharmacology
  • Spectrometry, Fluorescence
  • Staphylococcus hominis / drug effects*
  • Structure-Activity Relationship
  • Theranostic Nanomedicine
  • X-Ray Diffraction

Substances

  • Anti-Bacterial Agents
  • Manganese Compounds
  • Oxides
  • Citric Acid
  • manganese oxide
  • Folic Acid