Multidrug‐resistant (MDR) pathogenic bacterial infections have become a major danger to public health. Synergetic therapy through multiple approaches is more powerful than the respective one alone, but has been rarely achieved in defeating MDR bacterial infections so far. Herein, indocyanine green‐functionalized Mn3O4 nanosheets are engineered as an efficient and safe antibacterial agent with photothermal, photodynamic, and oxidase‐like activities, which display powerful ability in treating MDR bacterial infections. Therein, photothermal and photodynamic activities can be triggered by a single low‐powered near‐infrared laser (808 nm, 0.33 W cm−2), resulting in the generation of localized hyperthermia (photothermal conversion efficiency, 67.5%) and singlet oxygen. Meanwhile, oxidase‐like activity of this material further leads to the generation of hydroxyl radical as well as superoxide radical. Sheet‐like structure with rough surfaces make them tends to adhere on bacterial surface and thus damage membrane system as well as influence bacterial metabolism. As a result, Gram‐positive and Gram‐negative bacteria can both be eradicated. Animal experiments further indicate that the functionalized Mn3O4 nanosheets can effectively treat methicillin‐resistant Staphylococcus aureus‐infected wounds through the triple synergetic therapy. Moreover, toxicity evaluation in vitro and in vivo has proved the superior biosafety of this material, which is promising to apply in clinical anti‐infective therapy.

Functionalized Mn3O4 Nanosheets with Photothermal, Photodynamic, and Oxidase‐Like Activities Triggered by Low‐Powered Near‐Infrared Light for Synergetic Combating Multidrug‐Resistant Bacterial Infections

Advancement of Chitin and Chitosan as Promising Biomaterials

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.

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

Copper, the essential element required for the human body is well-known for its profound antibacterial properties, yet salts and oxides of copper metals in the copper mine tailings are reported to be a big burden in the modern era. Among other copper oxides, CuO, in particular, is known to have beneficial effects on humans, while its slight nanoengineering viz., surface functionalization of the nanometer-sized oxide is shown to make some paradigm shift using its inherent redox property. Here, we have synthesized nanometer-sized CuO nanoparticles and functionalized it with a citrate ligand for an enhanced redox property and better solubility in water. For structural analysis of the nanohybrid, standard analytical tools, such as electron microscopy, dynamic light scattering, and X-ray diffraction studies were conducted. Moreover, FTIR and UV-VIS spectroscopy studies were performed to confirm its functionalization. The antibacterial study results, against a model bacteria (S. hominis), show that CuO nanohybrids provide favorable outcomes on antibiotic-resistant organisms. The suitability of the nanohybrid for use in photodynamic therapy was also confirmed, as under light its activity increased substantially. The use of CuO nanoparticles as antibiotics was further supported by the use of computational biology, which reconfirmed the outcome of our experimental studies. We have also extracted CuO nanogranules (top-down technique) from copper mine tailings of two places, each with different geographical locations, and functionalized them with citrate ligands in order to characterize similar structural and functional properties obtained from synthesized CuO nanoparticles, using the bottom-up technique. We have observed that the extracted functionalized CuO from copper tailings offers similar properties compared to those of the synthesized CuO, which provides an avenue for the circular economy for the utilization of copper waste into nanomedicine, which is known to be best for mankind.

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Development of Nanomedicine from Copper Mine Tailing Waste: A Pavement towards Circular Economy with Advanced Redox Nanotechnology

Chemoprevention of bilirubin encephalopathy with a nanoceutical agent

A crucial balance between oxidative eustress and distress is important for maintaining redox homeostasis in the cellular milieu. Therefore, sustaining the intracellular redox buffer condition with exogenous agents could be a therapeutic strategy against diseases caused by redox imbalance. Here, we synthesized chitosan-functionalized Mn3O4 nanoparticles (Ch-Mn3O4 NPs) and tested their redox buffering capability in in-vitro and in-cellulo. Chitosan is easily absorbed by the intestine and can be used as a target-specific delivery agent to the intestine, while Mn3O4 NPs have redox modulatory properties. Therefore, combination of chitosan and Mn3O4 NPs provide the opportunity for targeted redox buffering. Targeted delivery of a drug and remediation of the corresponding indication qualify the drug to be a theranostic agent. Our spectroscopic studies suggest ROS generation as well as antioxidant ability of Ch-Mn3O4 NPs. In-cellulo studies using A549 cell lines confirmed the efficacy of the nanohybrid in redox homeostasis. The outcomes suggest that Ch-Mn3O4 nanohybrid has the potential to function as a target-specific redox buffering agent in both in-vitro and in-cellulo systems.

Synthesis and spectroscopic characterization of a target-specific nanohybrid for redox buffering in cellular milieu

This study explores a combined electrochemical and spectroscopic approach to investigate the degradation of bilirubin, a molecular marker of jaundice in humans using a biocompatible nanohybrid (citrate‐functionalized Mn3O4 nanohybrid; C−Mn3O4 NH). The approach is aimed at the development of a facile theranostic tool for treatment, detection, and prognosis of jaundice. Linear sweep voltammetry (LSV) studies on bilirubin, C−Mn3O4 NH, a model carrier protein, and its complex with bilirubin reveal the efficacy of the nanohybrid for both degradation and detection of bilirubin. Furthermore, spectroscopic studies depict that distal electron transfer to be the probable mechanism behind the observed bilirubin degradation in physiological milieu.

Interaction of a Jaundice Marker Molecule with a Redox‐Modulatory Nano‐Hybrid: A Combined Electrochemical and Spectroscopic Study toward the Development of a Theranostic Tool

The Front Cover shows the dual efficacy of an indigenously developed smart functionalized Mn3O4 nanohybrid (nano-doctor) for the detection of a jaundice marker, bilirubin, in an electrochemical setup and remediation of the toxic bilirubin through generation of reactive oxygen species (ROS) by the nano-doctor. Simultaneous detection and remediation of a disease by the nano-doctor is in a class of contemporary theranostics. A series of detailed preclinical studies from the research group revealed the potentiality of remediation of neurotoxicity, CKD, and liver fibrosis without any side effect. More information can be found in the Research Article by Samir Kumar Pal et al.. 

Front Cover: Interaction of a Jaundice Marker Molecule with a Redox‐Modulatory Nano‐Hybrid: A Combined Electrochemical and Spectroscopic Study toward the Development of a Theranostic Tool (ChemMedChem 14/2022)

Anirudddha Adhikari

Papers

Synthesis and spectroscopic characterization of a target-specific nanohybrid for redox buffering in cellular milieu

Interaction of a Jaundice Marker Molecule with a Redox‐Modulatory Nano‐Hybrid: A Combined Electrochemical and Spectroscopic Study toward the Development of a Theranostic Tool

Front Cover: Interaction of a Jaundice Marker Molecule with a Redox‐Modulatory Nano‐Hybrid: A Combined Electrochemical and Spectroscopic Study toward the Development of a Theranostic Tool (ChemMedChem 14/2022)