Abstract
<p>Cancer nanotechnology is a groundbreaking interdisciplinary area of science which is highly crucial in molecular imaging, diagnosis, and targeted therapies. The basic rationale of nanotechnology in oncology is the ability to improve drug solubility, increase drug halflife, and improve drug accumulation at the cancerous site. The Enhanced Permeability and Retention (EPR) effect leads the nanoparticles to accumulate in the tumor tissues reducing the adverse side effects of chemotherapeutic agents. However, most of the currently used nanoparticles are not compatible with the health and environmental safety aspects. Thus, this dissertation discusses the non-toxic, biocompatible, photoluminescent, semiconductor nano-motif of carbon dots(C-dots), and its active engagementsin various oncology studies, mainly in the brain oncology. Moreover, later in the chapters, C-dots are proposed as a nano-cargo for Alzheimer’s disease.<p/>
<p>Chapter 2 discusses the top-down synthesized black C-dots and their bone-related labeling ability by using qualitative zebrafish analysis. Moreover, the carbon dots were conjugated with ligands, such as glutamic and poly glutamic acids, which have been reported to have a high affinity for calcified sites. <p/>
<p>Chapter 3-6 address the brain oncology studies of black C-dots’ conjugates. Chapter 3 introduces two chalcone derivatives for the effective treatments of glioblastoma brain tumors. Moreover, enhanced efficacy of the two chalcones was reported after conjugating them with -COOH functionalized black C-dots along with transferrin. Transferrin played a vital role as the blood-brain barrier (BBB) targeting ligand, which is highly essential in brain tumors due to the inability of most of the conventional drugs to cross the BBB. By taking the knowledge gained from chapter 3, chapter 4 describes a triple conjugated nanocargo system of C-dots which carries two chemotherapeutics along with transferrin. The results revealed the high efficacy of the triple conjugated system on brain tumors than single conjugated systems and free drugs. As a follow up of chapter 4, in chapter 5, a quadruple conjugated C-dots system was introduced for brain tumors. The quadruple conjugate consists of two chemotherapeutics, along with two peptides attached to C-dots. The lnPep-1 is the receptor-targeted peptide which binds to the receptor of IL-13Rα2, which is only present on glioblastoma brain tumors. The nucleus targeted lnPep-1 facilitates the penetration of the nucleus membrane and localizes the chemotherapeutics in the nucleus. Chapter 6 reports a comparison of pH triggered doxorubicin releasing profiles of three different C-dots conjugates, which entails of acid cleavable hydrazone and disulfide bonds. The results revealed the efficacy of two acid-cleavable linkages than the direct doxorubicin conjugation on C-dots while suggesting that, in the acidic tumor microenvironment, the acid-cleavable linkages will acquire higher and sustained drugreleasing profiles than the direct conjugations.<p/>
<p>Chapter 7 introduces C-dots as a multi-drug nanocarrier for the treatments of Alzheimer’s disease. A triple conjugated C-dots system was introduced to target two etiologies of AD simultaneously. Thus, the C-dots can be conjugated with amyloid and non-amyloid diagnostics along with the BBB targeting ligand transferrin. As a preliminary step, the C-dots were conjugated with the acetylcholine inhibitor, tacrine, along with transferrin.<p/>