Design of Luminescent Magnetic Nanostructures for Sensor, Drug Delivery and Bioimaging Applications

Abstract

The present dissertation entitled, “Design of Luminescent Magnetic Nanostructures for Sensor, Drug delivery and Bioimaging Applications” is an embodiment of the investigations intended at developing simple inexpensive synthetic methods for producing luminescent carbon quantum dot and multifunctional magnetic luminescent nanostructures applicable for sensor and biomedical application. The in vitro applications of synthesized materials have also been investigated. The thesis is divided into two parts. The first part of the thesis includes the low cost synthetic route for fabrication of carbon quantum dots (CD) and their composites for sensing and bioimaging applications. Highly photoluminescent CDs with a quantum yield of 26% have been synthesized in one step by hydrothermal treatment of orange juice (Citrus nobilis deliciosa). Due to high photostability and low toxicity these CDs have been demonstrated as excellent probes in cellular imaging. These synthesized CD has been also used for the development of reusable novel magnetic silica/CD based hybrid nanostructure for monitoring and separation of fluoride ion through fluorescence sensing and external magnetic field respectively. The assay is based on the binding of fluoride ion into magnetic receptor substituting already bound CD. This method is highly sensitive, fast and selective for fluoride ion in aqueous solution having a linear response range of 1 to 20 μM (R2=0.992). The practical utility of the method is well tested with tap water and also extended for fluoride detection in cellular environment. Furthermore an easily separable sensitive CD based fluorescence glucose sensor comprising of CD deposited mesoporous silica nocomposite (m-SiO2-CD) and 3-aminophenylboronic acid (APBA) has been prepared. The observed fluorescence recovery of quenched APBA adsorbed m-SiO2-CD on addition of glucose is due to the formation of glucoboronate ester which could lift out the APBA from close vicinity of fluorophore. The boronic acid modified (m-SiO2-CD-APBA) fluorescent probe is also explored for targeted imaging of colon cancer cell overexpressed with sialyl Lewis A (sLea) receptors. To improve the luminescence properties of the CD, nitrogen, sulphur co-doped carbon quantum dot (NSCD) with an improved fluorescent quantum yield of 69% have been synthesized from single molecular precursor. The synthesized NSCD exhibits high selectivity and sensitivity towards mercury ion in aqueous environment. Due to high photostability, low toxicity and low detection limit as 0.05 nM, these NSCDs are demonstrated as excellent probes for the detection of Hg2+ in living cells.The second part of this thesis demonstrates the design and fabrication of multifunctional fluorescent magnetic nanostructures which are of special interest in cancer diagnostic and therapy. Multifunctional luminescent magnetic Fe3O4@mesoporous silica-YPO4:Tb core-shell nanoparticle has been prepared for the storage as well as controlled targeted release of 5-fluorouracil (5-FU). The hydrophobic anticancer drug 5-FU has been successfully loaded on the fluorescent magnetic nanoparticles via formation of 5-FU/β-cyclodextrin inclusion complex which favors more sustained release at lower pH owing to stability of inclusion complex. These findings show that the developed multifunctional nanocomposite can be potentially used in magnetically guided delivery of 5-FU. Furthermore, hierarchical theranostic hollow magnetic mesoporous spherical particles with fluorescent carbon encapsulated within mesoporous framework have been prepared by hydrothermal carbonization approach. These fluorescent magnetic nanoparticles have been conjugated with hydrophobic drug camptothecin and a molecular marker folic acid using appropriate surface chemistry to ensure the targeted specific delivery of the camptothecin. The drug conjugated hybrid nanoparticles inhibit cell growth through induction of apoptosis as demonstrated in HeLa cells. In addition to this, the particles show MR contrast behaviour by affecting the proton relaxation with transverse relaxivity (r2) 150.03 mM-1S-1.