Phytochemical(s)-functionalized Molybdenum Oxide in Theranostics: Bio-Nanointerfaced System for Cellular Oxidative Stress Control and Inflammatory Biomarker Detection

<p dir="ltr">The work presented in this thesis investigates the intricate relationship between oxidative stress and inflammation, two critical factors contributing to a wide range of chronic diseases. This investigation is particularly important due to the pervasive nature of these processes in different disease pathophysiology. The perpetual cycle between oxidative stress and inflammation is crucial in disease mechanisms. ROS can activate inflammatory pathways, and inflammatory cells produce additional ROS, exacerbating oxidative stress. This vicious cycle leads to sustained cellular damage and chronic disease progression. Detecting inflammatory biomarkers is vital for diagnosis and early treatment of diseases. Biomarkers like cytokines (e.g., interleukin-6 and prostaglandin E2) indicate the presence and extent of inflammation, helping in the assessment of disease activity and therapeutic responses. Despite advancements, challenges remain in effectively targeting oxidative stress and inflammation. Current therapeutic strategies often fall short due to the complexity of these processes and the need for precise, targeted interventions. The thesis addresses critical and potential issues in the development of theranostics using phytochemical-functionalized molybdenum oxide nanoparticles (MoOx NPs) and to explore them as a noval theranostics for managing oxidative stress and inflammation. This approach combines diagnostic and therapeutic capabilities, aiming to improve the detection and management of oxidative stress and inflammation through advanced nano-theranostics. This research advances the understanding of the oxidative stress-inflammation nexus and proposes innovative solutions using MoOx NPs. To address these aims, four main objectives were drawn: </p><p dir="ltr">• Synthesis of MoOx Nanostructures: Exploring different synthesis strategies to create molybdenum oxides with varying morphologies and functionalizing them with phytochemicals for theranostic applications. </p><p dir="ltr">• Real-Time Responsiveness: Investigating the real-time behavior of these nanostructures under oxidative stress conditions at the bio-nanointerface. </p><p dir="ltr">• Biocompatibility and ROS Scavenging: Assessing the biocompatibility and ROS scavenging properties of the prepared nanosystems, along with their anti-inflammatory properties. </p><p dir="ltr">• Electro/Opto Chemical Biosensing: Demonstrating the biosensing performance of phyto-functionalized MoOx nanosystems for inflammation biomarkers. </p><p dir="ltr">This thesis provides an overview of the link between cellular oxidative stress and inflammation, emphasizing the potential of nanotheranostics, particularly metal-polyphenol systems, in targeting these conditions (Chapter 1). Starting with prime objectives focuses on the synthesis of MoO3 nanoparticles hybridized with kaempferol. This chapter highlights the nanoparticles' capabilities in ROS scavenging and electrochemical immunosensing of interleukin-6 (IL-6), demonstrating their multifunctional theranostic potential (Chapter 2). Distinctly, these MoHK NPs exhibit a clinically significant antioxidant function and cytocompatibility with RAW 264.7 macrophage cell line. Bioaffinity layer assisted monoclonal antibodies of IL-6 immobilized on MoHK electrode enable superior selectivity, electrochemical signal transduction. However, as the most of cellular assays performed are end-point detection of cellular state at time course. Thus, fingerprint the nano-bio interfaces behaviour in non-invasive environment for real-time monitoring has been established using Electric Cell-Substrate Impedance Sensing (ECIS) system for understanding the biophysical and cellular state. This system helps in non-invasive monitoring of oxidative stress and evaluating the healing effects of nanoparticles (Chapter 3). Moving further, this thesis describes the development of MoO3 quantum dots functionalized with 2-hydroxypropyl-β-cyclodextrin. These quantum dots are versatile nanoprobes for ROS detection, bioimaging, and ultra-sensitive detection of prostaglandin E2 (PGE2), which plays a crucial role in inflammation (Chapter 4). This thesis further investigates the role of oxidative stress in chronic inflammatory diseases like Inflammatory Bowel Disease (IBD) and develops an electrochemical immunosensor for oxidative stress biomarkers. The sensor's clinical applicability is validated using samples from IBD patients (Chapter 5). At last, this thesis focuses on targeting the pivotal marker involved in initiating the inflammation by developing MoO3 2D nanosheets decorated with tannic acid (Chapter 6). Ending the thesis with the summary of the findings, contextualization with existing literature, and discussing the beginning of future potential of the developed theranostics platform in managing inflammation (Chapter 7). The research presented in the thesis significantly advances the understanding of inflammation management using nano-theranostics, demonstrating their efficacy in ROS scavenging and inflammation sensing with a focus on key biomarkers. This work not only provides insights into the material science aspects but also highlights the practical implications in clinical settings.</p>