DEVELOPMENT OF CARBON DOTS BASED MULTIFUNCTIONAL NANOMATERIALS FOR POTENTIAL APPLICATIONS

Abstract

The discovery of fluorescent nanomaterials has been an important breakthrough in the ever expanding field of nanotechnology. With remarkable optical and chemical properties, fluorescent nanomaterials have been perceived as potential substitutes for organic dyes. Their exciting properties make them one of the most useful tools that chemistry has produced for biological purposes. Nanosized carbon dots (C-dots) have been the latest addition to the family of fluorescent nanomaterials which have enormous potential for application in diverse fields, ranging from analytical to biomedical. Besides, the versatile nature of C-dots can be exploited for creating multifunctional nanomaterials by combining them with drugs or nanoparticles. Such materials combine the therapeutic and imaging aspects in one entity for implementing multimodal functionality in biomedical applications. Hence, this thesis presents unique synthetic schemes for producing strongly fluorescent C-dots which have been further evaluated for their prospective applications. Furthermore, the development of C-dots based metal/hydrogel multimodal hybrid assemblies for anticancer and antioxidant applications has also been explored. In Chapters 1-3, introduction, literature review and experimental procedures have been elucidated. In chapter 4, a unique approach has been devised, wherein, polyethylene glycol (PEG) and polyethyleneimine (PEI) passivated C-dots have been synthesized by one-step hydrothermal carbonization of chitosan. A comparative analysis of physicochemical and bioimaging properties of PEI based C-dots (CD-PEI) and PEG based C-dots (CD-PEG) was carried out. Further, the role of surface functionality was evaluated to gain an insight into the bioimaging efficiency of CD-PEI compared to CD-PEG. In chapter 5, another interesting approach for synthesizing C-dots through green synthetic route was adopted. To this end, one-step hydrothermal treatment of coriander leaves was performed for preparing self passivated C-dots, without the aid of auxiliary passivating agent. These C-dots were further used as a fluorescence probe for sensitive and selective detection of Fe3+ ions. Eventually, the bioimaging and antioxidant potential of C-dots was evaluated through a variety of analytical assays. Therefore, the practicality of C-dots obtained from a herbal carbon source for versatile applications was validated. In chapter 6, cerium oxide (CeO2) based nanocomposite (NC) integrating fluorescent C-dots were synthesized by hydrothermal method. The antioxidant potency of CDs-CeO2 NC was iv evaluated in NIH3T3 fibroblast cells treated with H2O2, a major reactive oxygen species (ROS) responsible for oxidative stress. Tracking the intracellular fluorescence of CDs-CeO2 NC by microscopy and flow cytometry made it possible to examine the capabilities of CeO2 for abatement of H2O2-mediated oxidative stress, whilst monitoring their uptake. C-dots based metal NCs constitute fascinating imaging and therapeutic tools for anticancer applications. In chapter 7, C-dots were integrated with silver@zinc oxide to form CD-Ag@ZnO NC. Accordingly, the ability of CD-Ag@ZnO NC in tracking the cellular uptake and mediating apoptotic effects was demonstrated against MCF-7 (breast cancer) and A549 (lung cancer) cells. By monitoring the green fluorescence emission of CDs, the cellular uptake and distribution of the CD-Ag@ZnO NC could be ascertained. Moreover, apoptosis induction in cancer cells treated with CD-Ag@ZnO NC was validated through morphological, biochemical and molecular studies. Multifunctional hydrogels offer a seemingly efficient system for delivery of drugs and bioimaging modalities. In chapter 8, chitosan based hydrogel formulation composed of highly fluorescent C-dots and loaded with an anticancer drug, 5-Fluorouracil (5-FU) was realized to form 5-FU@CD-HY. Multifunctional aspects of 5-FU@CD-HY in monitoring the cellular uptake and inflicting apoptosis were revealed by in vitro studies on A549 cells. Green fluorescence of CDs in 5-FU@CD-HY aided the qualitative and quantitative assessment of cellular uptake. Additionally, the fluorescence of CDs could be used to detect apoptosis instigated by 5-FU. Induction of apoptosis in 5-FU@CD-HY treated cells was evidenced by changes in cell cycle distributions, visualization of characteristic apoptotic bodies through FE-SEM and apoptotic gene expression studies. Keywords: C-dots, chitosan, hydrothermal, bioimaging, coriander, antioxidant, anticancer, nanocomposites, apoptosis, cerium oxide, reactive oxygen species, hydrogels.