Nanocomposites for Theranostic Applications
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Nanomaterials have immense potential to improve healthcare by designing simple, low cost biosensors, generation of the novel therapeutics and delivery of the therapeutics with enhanced efficacy by suitable cargo. My PhD thesis works are focused on synthesi zing and engineering nanomaterials, having dual characteristics of diagnostic and therapy i.e. theranostics, in order to address important issues of healthcare. The thesis is divided into seven chapters. Chapter 1 - Introduction and Review of Literature - describes the scholastic insights of the reports available in the literature related to the present work and involving synthesis and characterization of the different nanomaterials suitable for biomedical applications. Also, the context of the present thesis vis-à-vis current technological challenge in nanobiotechnology is elaborated. In Chapter 2, synthesis of a novel fluorescent Au NP- composite has been reported, based on reaction of reaction of paracetamol (p-hyrdoxy acetanilide) - a well-known anti-pyretic and analgesic molecule, generally considered as safe for human consumption- and HAuCl4. The Au NP-PD composite employed in detection of both Gram positive and Gram negative bacteria. Next aim was to develop a novel antibacterial agent effective against common bacterial strains. The Ag NPs has been found to be highly bactericidal against both Gram positive and Gram negative bacteria. Hence, the synthesis of Ag NP-PD composite by reaction of the AgNO3 and paracetamol was reported in Chapter 3. Interestingly, enhancement in the reactive oxygen species (ROS) generation was observed in presence of the composite. It is proposed that the ROS generation led to oxidation of the dimer to N-acetyl p-benzoquinone imine (NAPQI). The generated NAPQI acted as a DNA gyrase inhibitor causing bacterial cell death following linearization of DNA. The above findings opened up the hope that the paracetamol dimer along with suitable ROS generator would be a potential cancer therapeutic agent. Thus, in Chapter 4, the cytotoxic effect of PD along with the ‘few atoms’ silver nanoparticles of size less than 2 nm, commonly called as silver nanoclusters (NCs), is reported. To perform targeted delivery folic acid was conjugated with the chitosan and carried out the cytotoxicity study for different types of cancer cells. Next, one step simple aqueous synthesis of the Au NCs by using the biopolymer chitosan as template is reported in Chapter 5. The chitosan Au NC composite was converted into polymeric nanoparticles and used for the suitable bioimaging agents. In order to convert these fluorescent NPs as theranostic NPs, suicide gene (CD-UPRT) was loaded and delivered in cervical cancer cells (HeLa) for induction of cell death. In Chapter 6, a simple way of synthesis of highly fluorescent Au NCs was devised by exploiting the polymerase chain reaction (PCR) condition and amplified DNA as template was reported. As the Au NC was found to be non-cytotoxic, therefore, the method offers exceptional promises for synthesizing highly fluorescent Au NCs and concurrently estimating DNA amplification, which can be applied for designing devices. Chapter 7 summarizes overall thesis works and describes future prospects. In brief, the present thesis is aimed at synthesizing nanomaterials, which are useful for the biomedical applications. Some of the methods developed during the pursuit of the thesis have important future implications in bacterial estimation and annihilation, fluorescence based imaging and killing of cancer cells and quantitative estimation of gene expression.
Supervisor: Siddhartha Sankar Ghosh and Arun Chattopadhyay