Ultrasound driven synthesis of bio-functional nanostructures
AuthorBhangu, Sukhvir Kaur
AffiliationSchool of Chemistry
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-11-04.
© 2019 Sukhvir Kaur Bhangu
Polyphenolic-, amino acids- and doxorubicin-based nanostructures are of great interest due to their multifarious applications in biomedical field as antibiotics, antioxidants, antimicrobial and anti-cancer agents. Most of the research on the polyphenolic and amino acids based nanostructures adhere to the formation of coordination complexes with metals, self-assembly techniques or chemical functionalization and crosslinking reactions. To improve the efficacy of therapeutic agents, a variety of nanoparticles have been developed for the controlled and targeted delivery of doxorubicin. These include biopolymers-based nano/microcapsules, carbon-based nanoparticles, polymer-drug conjugate, dendrimers, liposomes, micelles, inorganic nanoparticles and nucleic acids nanostructures. The development of simple, one pot and effective synthesis routes to fabricate bio-nanomaterials is in high demand. In particular, the use of polyphenols, doxorubicin and single amino acids as building blocks to fabricate nanostructured materials is still unexplored. In this PhD work, I have used ultrasound-based technologies to synthesize phenolic, amino acid and doxorubicin based micro and nanoparticles for different biomedical applications. Chapter 1 provides an overview on the structural and bio-functional properties of nanoparticles and methods to synthesize nanoparticles for biomedical use, including the ultrasonic techniques have been discussed. Furthermore, fundamentals of ultrasound are also provided. In the literature review (Chapter 2), several studies dealing with the polyphenol, doxorubicin and amino acid molecules have been summarised. In the last section of this chapter, numerous investigations on synthesis of diverse types of nanostructures using ultrasound are reviewed. In Chapter 3 materials and methods, equipment and all other experimental details used are described. Chapter 4 provides a fundamental understanding on the ultrasonic coupling of simple phenolic molecules, where acoustic bubble acts as a catalytic binding site for the generation of bioactive oligomers without the need for utilizing any enzymes, catalysts (organic or inorganic) and other toxic reagents. It has been observed that the extent of oligomerization and nanoparticles formation depends on the ultrasonic frequency, concentration and physiochemical properties of the phenolic building blocks. Chapter 5 demonstrates that cavitation bubbles are simple micro-reactors with reactive surfaces to perform one-pot multiple reactions on complex polyphenolic molecules to convert tannic acid to ellagic acid, namely (i) hydrolysis of an ester linkage, (ii) C–C coupling reactions, (iii) condensation reactions and (iv) crystallization of the product into regularly shaped particles. The size and shape of the crystals can be controlled by ultrasonic frequency, power and time. The synthesized particles exhibit fluorescence properties, anticancer and antioxidant activity and could be further used for drug loading and delivery. In Chapters 6 and 7, the role of the acoustic field in the formation of supramolecular nanoaggregates using tryptophan and phenylalanine as building blocks was investigated. It has been demonstrated that the acoustic bubbles driven at high frequency standing wave, in addition to provide a reactive surface for the dimerization of biomolecules, can also provide an energy source to fuel and refuel the dissipative out of equilibrium assembly of these molecules below the critical aggregation concentration. Furthermore, the unique optical and bio-functional properties of nanoparticles for bioimaging and probing the intracellular trafficking of a drug have also been studied. In Chapter 8 the sound-driven self-assembly of the anticancer drug doxorubicin was investigated to generate nanoparticles solely made of drug molecules. The newly developed nanoparticles were tested on different types of cancer cells and the drug was found to be active in drug resistant cell lines. In addition, the mechanism of action of drug nanoparticles was investigated. Chapter 9 provides a summary of the entire PhD work.
KeywordsNanoparticles; Self-assembly; Polyphenols; Amino acids; Doxorubicin; Ultrasound; Tryptophan; Tannic acid; Ellagic acid; Phenylalanine; anticancer
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