Luminescent Heteroatom doped Carbon Quantum Dots for Sensing and Drug Delivery Applications

Abstract

The present dissertation entitled, “Luminescent Heteroatom doped Carbon Quantum Dots for Sensing and Drug Delivery Applications” is an embodiment of the investigations aimed at developing simple inexpensive synthetic methodologies for producing heteroatom doped carbon quantum dots pertinent for sensing and biomedical application. The diagnostic and therapeutic applications of these multifunctional nanomaterials have been studied in vitro. The thesis has been divided into seven chapters.
Hydrophilic boronic acid modified nitrogen sulphur doped carbon quantum dots (BNSCQD) have been prepared following a cost effective hydrothermal approach. The co-doping is aimed to improve the luminescence as well as targeting affinity of the CQD. Due to intense fluorescence property, appreciable photostability, boronic acid functionality and low cytotoxicity the carbon quantum dots (CQD) have been utilised in sensing glucosamine and cancer cell receptor Sialyl Lewisa (SLa). This method is highly sensitive and selective for visual detection of glucosamine sensing using a paper based sensor strip. Furthermore, integration of dopamine with BNSCQD (BNSCQD-Dopa) sets a platform for development of a fluorescence turn-on nanoprobe for fluoride detection in real samples. Due to boron’s affinity towards fluorine, the system was very selective towards fluoride when compared with other anions with a detection limit 0.7 pM. The practical ultrasensitive utility of the sensor is well demonstrated in human serum samples and also extended for fluoride detection in cellular environment. Further, the BNSCQD has been integrated with gadolinium iron oxide and mesoporous silica to construct a theranostic nanoparticle where BNSCQD imparts multiple functions such as simultaneous pH-sensitive gate opening, leading to control drug release, optical imaging, and receptor targeted internalization of the theranostic particle. The drug release experiment under variable pH and in the presence of competitive binding ligand SLa clearly shows the excellent responsiveness of the BNSCQD capped MSN hybrid system toward dual stimuli. Because of reasonably good r1 r2 relaxivities of the magnetic core and excellent fluorescence property of the doped carbon quantum dot, the hybrid can be utilized to monitor the therapeutic response through MRI and/or fluorescence imaging. Nitrogen doped mesoporous hollow carbon nanospheres (NCQD-HCS) have been prepared by inert calcination of polymer synthesized using pyrrole, aniline and Triton X-100 as molecular precursors. Here a direct synthetic approach is followed to yield high surface area carbon spheres with fluorescence property. An optimization of both surface area and photoluminescence is achieved by tuning temperature of calcination. The highest PL quantum yield of 14.6% is recorded, which is suitable for confocal imaging of cells. The fluorescence property of these spheres is attributed to the embedded nitrogen doped carbon quantum dots (NCQD) in carbon matrix. The photothermal property of NCQD-HCS has been investigated under 980 nm NIR irradiation. Cell killing efficacy of hollow spheres by photothermal ablation effect is evaluated in FaDu cells (oral cancer) as a modal cell line. Similarly, the upconversion property of carbon spheres is explored for light responsive drug release of gemcitabine. A highly biocompatible click chemistry based gating system is designed to restrict the premature release of drug molecules from porous nanospheres. The utilization of upconverted radiation by substituted nitrobenzyl linker, initiating its cleavage followed by drug release under periodic irradiation (980 nm laser) intervals has been tested in vitro. These fluorescent multifunctional nanoparticles provide a platform for combinatorial therapy of oral cancer.