HALLOYSITE CLAY NANOTUBES FOR BIOMEDICAL AND INDUSTRIAL APPLICATIONS: OPTIMIZATION OF THEIR PHYSICO-CHEMICAL PROPERTIES.
Tesi di Dottorato
Data di Pubblicazione:
2020
Citazione:
HALLOYSITE CLAY NANOTUBES FOR BIOMEDICAL AND INDUSTRIAL APPLICATIONS: OPTIMIZATION OF THEIR PHYSICO-CHEMICAL PROPERTIES / K.f. Fidecka ; supervisor: E. Licandro; co-supervisor: R. Vago (San Raffaele Hospital). Università degli Studi di Milano, 2020 Jan 23. 32. ciclo, Anno Accademico 2019. [10.13130/fidecka-katarzyna-fidecka_phd2020-01-23].
Abstract:
Present PhD thesis aimed to investigate relatively unknown properties of halloysite nanoparticles, as well as to further examine HNTs as potential drug nanocarriers. NPs loading and release characteristics were studied using model active molecules: magnesium monoperoxyphthalate (MMPP), aspirin and epirubicin. The research was fulfilled with formation of complex multi-functional nanoarchitectures, which apart from ability to deliver incorporated drugs, showed the potential of controlled and sustain release of therapeutics, biocompatible and bioresorbable characteristics as well as potential targeting abilities. Great attention was dedicated to characterization of formed halloysite-based nanoarchitectures in qualitative as well as quantitative manner. Investigations performed in this thesis also faced the problem of exceeding dimensions of halloysite units, nanoparticles aggregation, poor loading capability and dose dumping effect. Subsequently, studies for trying to find a solution to these obstacles were undertaken. Fully characterized halloysite nanoconstructs were further examined in biological field, employing different cancer cell lines. Studies on pristine halloysite nanotubes: Physico-chemical and biological properties of halloysite nanoparticles were evaluated using microscopic techniques, spectroscopic analysis, surface studies regarding charge, porosity and wettability. The thermal and time-based examination of pristine halloysite was performed as well, showing stability of HNTs alumino-silicate skeletons up to ~400 ℃ and over a long period of time (2 years) at room temperature, however with a variable amount of incorporated water molecules. Biological performance of HNTs was determined in vitro in multiple cellular systems by toxicity, cellular uptake, colocalization and accumulation studies using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] tetrazolium reduction (MTT) assay and set of microscopic techniques. Aiming to deeply characterize halloysite nanoparticles, the study proceeded with employment of non-standard techniques, as multiphoton microscopy that drove to discovery of novel NPs promising capabilities. It was revealed that halloysite is able to convert light to its second harmonic, at twice of the frequency (and therefore half of the wavelength) while using high intensity femtosecond pulsed laser. Halloysite Second Harmonic Generation (SHG) signal was detected over a broad wavelength range, showed stability over a long period of time, polarization properties and quadratic dependence on the intensity of incident light. The analysis also pointed out characteristic structure properties of the nanoparticle that is lack of the center of symmetry and the high crystalline structure organization. Among a wide spectrum of domains where discovered HNTs characteristics can be utilized (e.g. optoelectronics, biosensors), we have explored its application in alternative label-free bioimaging. The proposed multiphoton method of analysis showed advantages over the standard confocal microscopy, since e.g. nanoparticles did not have to be stained prior the analysis, thus no possible alterations of HNTs including size, surface chemistry and consequent cellular uptake were induced. Therefore, for the first time, halloysite nanotubes were exploited as imaging agents, taking advantage of their endogenous properties. Along the research it was revealed that the length of pristine HNTs and the strong aggregation limit their ability to pass intracellular membranes and thus minimize their effectiveness as drug nanocarriers. Therefore, efforts were devoted to the development of facile methodology to efficiently disperse and shorten HNTs units. Set of characterizations techniques, such as Scanning Electron Microscopy (S
Tipologia IRIS:
Tesi di dottorato
Keywords:
nanotechnology; halloysite nanoparticles; drug delivery; physico-chemical characterization; imaging; biomedical and industrial applications
Elenco autori:
K.F. Fidecka
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