Summary and future scope
113 7.1 Summary
The doping of heteroatom in carbon quantum dots provides improved photophysical and chemical properties for its application in ultrasensitive sensing and targeted treatment of human cancer cells. With respect to this, the work addressed in this doctoral thesis addresses development of some smart multifunctional carbon quantum dots which can be used for the detection of biologically important agents and administration of widely accepted anticancer drugs like 5-fluorouracil and gemcitabine. The luminescence properties of these nanoparticles opens the possibility for monitoring the therapeutic response through fluorescence and MRI based bioimaging. The major findings of the present thesis work are as follows:
Highly luminescent, B, N, S doped carbon quantum dots have been synthesized by one step hydrothermal approach. The BNSCQD probe strongly binds to glucosamine at nanomolar levels with a detection limit of 0.75 nM. To the best of our knowledge, this is the only quantum dot based sensor operating in the visible region for the detection of glucosamine at the nanomolar level.
A simple fluorescence turn on sensor for the detection of fluoride ion in totally aqueous medium at neutral pH has been developed by integrating boronic acid functionalized carbon quantum dot (BNSCQD) and dopamine. This CQD sensor was successfully used in real samples and human serum samples. Cellular toxicity test showed that BNSCQD possess low toxicity. Our fluorescence sensor can efficiently be used to monitor fluoride contamination inside the cell.
A novel type of multifunctional hybrid nanoparticle composed of magnetic gadolinium oxide-iron oxide core, mesoporous silica shell gated with BNSCQD has been constructed. The overall size of this theranostic construct is 42 nm and it is highly stable in aqueous medium. The recognition and fluorescence turn on response of BNSCQD toward cell surface glycan sialyl Lewisa (SLa) enables targeted drug release and excellent fluorescence imaging of SLa overexpressed HepG2 cancer cells.
N-doped mesoporous hollow carbon spheres have been synthesized using polyaninile- co-polypyrrole block polymers. These mesoporous carbon hollow spheres were efficient in generating localized thermal ablation effect in FaDu cells, under a 980 nm laser irradiation. Impressive fluorescence property of these nanospheres allows in vitro imaging of cancer at different excitation wavelengths.
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N-doped mesoporous hollow carbon spheres acts as an excellent carrier for loading hydrophobic anticancer drug gemcitabine. The substituted nitrobenzene organic linker gate tightly holds the drug in the mesoporous network and minimises the possibility of premature drug release. Such a theranostic nanoparticle shows elevated cell killing effect due to combined chemotherapeutic and photothermal therapy.
7.2. Future scope
Although there are many exciting potential biomedical applications of luminescent heteroatom doped carbon quantum dots, considerable challenges and issues remain to be resolved. Some issues such as the exact origin of fluorescence, the role of dopant ions, and their location in CQD were not resolved yet. Thus, these issues should be addressed for fundamental understanding and tuning the luminescence properties of doped CQD. So far for the recovery of CQD from reaction medium tedious techniques like column chromatography and/or dialysis are adopted. The scaling up of the fabrication techniques is the most important for their practical pharmaceutical applications.
Inventive design of NIR responsive nanocarriers has allowed unprecedented control over the drug delivery process through the use of NIR radiation with deep tissue penetration.
However, investigation on the toxicological properties of materials needs more careful examination of the nanocarriers circulation, accumulation and metabolism, to give researchers a more systematic understanding of the fate of materials in the body.
Complexity of biological systems restricts nanoparticles with a single therapeutic effect and often fails to meet their purpose, leading to problems such as drug resistance. ROS generating properties of carbon nanomaterials has recently been explored. Hence the developed multifunctional theranostic materials can be evaluated for their possible application in photodynamic therapy.
List of Publications Thesis related publications
(1) R. K. Das and S. Mohapatra, Highly luminescent, heteroatom-doped carbon quantum dots for ultrasensitive sensing of glucosamine and targeted imaging of liver cancer cells, Journal of Materials Chemistry B, 2017, 5, 2190-2197. (Citations: 32) RSC (Most cited original research article 2017)
(2) R. K. Das, A. Pramanik, M. Majhi, and S. Mohapatra, Magnetic mesoporous silica gated with doped carbon dot for site specific drug delivery, fluorescence and MR imaging, Langmuir, 2018, 34, 5253-5262. (Citations: 9) ACS
(3) S. Mohapatra and R. K. Das, Novel hetero atom doped carbon quantum dot probe for fluorescence detection of fluoride ion in total aqueous medium, Analytica Chimica Acta, 2019, 1058, 146-154. ELSEVIER
(4) Synthesis and Characterization of Heteroatom Doped Hollow Carbon Spheres for Fluorescence Imaging and Photothermal Therapy of Cancer. (manuscript submitted) (5) Upconverting Mesoporous Carbon Nanospheres with Light-responsive Molecular
Gate for Gemcitabine Delivery and Fluorescence Imaging. (manuscript under preparation)
Additional publications
(1) S. Mohapatra, S. R. Rout, R. K. Das, S. Nayak and S. K. Ghosh, Highly hydrophilic luminescent magnetic mesoporous carbon nanospheres for controlled release of anticancer drug and multimodal imaging, Langmuir, 2016, 32, 1611-1620. (Citations:
43) ACS
(2) R. K. Das, J. P. Kar and S. Mohapatra, Enhanced photodegradation of organic pollutants by carbon quantum dot (CQD) deposited Fe3O4@mTiO2 nano-pom-pom balls, Industrial & Engineering Chemistry Research, 2016, 55, 5902-5910.
(Citations: 10) ACS
(3) S. Mohapatra, M. K. Bera, and R. K. Das, Rapid "turn-on" detection of atrazine using highly luminescent N-doped carbon quantum dot, Sensors and Acutators B, 2018, 263, 459-468. (Citations: 9) ELSEVIER
Achievements
(1) “Best Oral Presentation Award” at World Congress on Drug Discovery and Development 2016, BioGenesis Health Cluster at Indian Institute of Science, Bangalore.
(2) “ISNM-BC (Beckman Coulter) Industrial Best Poster Award” at Nanobioteck 2017 (Indian Society of Nanomedicine-AIIMS Delhi), Indian Institute of Science Education and Research, Thiruvananthapuram.
(3) “Best Research Poster Award” in Department of Chemistry, National Institute of Technology, Rourkela at Research Scholars Week 2018.