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Smart and Multifunctional Core-Shell Nanoparticles (NPs) for Drug Delivery

Bandyopadhyay, Sulalit
Doctoral thesis
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2016-294_Bandyopadhyay_Sulalit_PhD.pdf (Locked)
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URI
http://hdl.handle.net/11250/2423731
Date
2016
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Abstract
Nanomaterials designed for drug delivery applications require important properties that include

monodispersity, biocompatibility, long circulation time which are dependent on size, shape,

composition, surface charge among others. Incorporation of targeting and imaging modalities

into such nanomaterials allows for both therapeutic and diagnostic functions. Au nanoparticles

(NPs), besides being biocompatible, are known to show remarkable optical properties, widely

exploited for both bio-sensing and imaging. Setting in of anisotropy causes a wider frequency

response range in terms of plasmonic properties, making them promising candidates for

hyperthermia. On the other hand, Fe NPs display superparamagnetic properties that can be used

for targeting as well as imaging based on magnetic resonance.

Another field of nanomaterials that has garnered interest in recent times is stimuli sensitive

hydrogels that swell and collapse in response to temperature and/or pH. These entropically

driven volumetric transitions enable release of the cargo as a function of changing stimuli,

making them promising candidates for controlled release.

Combination of nanomaterials leads to synergistic enhancement of properties stemming from

their respective counterparts. Core-shell NPs is one such combination that has been studied in

this work. The main focus of this thesis has been to synthesize, characterize and functionalize

core-shell NPs with an aim to use these nanomaterials for theranostic (therapeutic and

diagnostic combined) applications. In this pursuit, core-shell Fe@Au NPs, anisotropic Au NPs,

poly(N-isopropylacrylamide) (pNIPAM) based hydrogels and hybrid NPs formed by

combination of metallic NPs and hydrogels have been studied. The physico-chemical

properties of these NPs have been mapped using a wide array of characterization techniques.

Size measurements have been done using dynamic light scattering (DLS) and scanning

transmission electron microscopy S(T)EM. The plasmonic properties of Au have been

characterized primarily using UV-Vis spectroscopy while surface properties of the NPs have

been tracked using electrophoretic mobility measurements, X-ray photoelectron spectroscopy

(XPS) among other techniques.

Different hybrid NPs have been loaded with model protein drug Cytochrome-C or L-Dopa, a

drug administered for Parkinson’s disease, in order to understand the effects of size, shape,

particle number density, drug-carrier interaction, response to stimuli on both loading and

release. Release kinetics have been modelled in order to understand the conformational changes

in the NPs leading to effective release of the drug.

Fe@Au NPs have been shown to have negligible cytotoxic effects on different cell lines, in

addition to their remarkable magnetic and optical properties. In order to further modify the

optical properties, anisotropic Au NPs have been synthesized to understand their growth

mechanisms. Five differently shaped Au NPs have been thereafter functionalized to assess their

cytotoxicity on cancer cells and also to understand the role of shape in the release kinetics of a

model protein drug. One of the main findings from the thesis work is that incorporation of

metallic NPs inside temperature and/or pH sensitive hydrogels enhances drug loading

capacities. In addition, the loaded drug is squeezed out at a faster rate from these systems when

the hydrogel units collapse above volume phase transition temperature (VPTT). The swellingcollapse

properties of the hydrogels have been captured using a robust methodology developed

for the determination of VPTT. A predictive reversibility parameter has been defined for the

first time taking all the system state points into consideration. Thus, the NPs studied within

the scope of this work provide an incremental contribution to the ever expanding search for

smart materials for drug delivery applications.
Has parts
Paper 1: Bandyopadhyay, Sulalit; Singh, Gurvinder; Sandvig, Ioanna; Sandvig, Axel; Mathieu, Roland; Kumar, P Anil; Glomm, Wilhelm. Synthesis and in vitro cellular interactions of superparamagnetic iron nanoparticles with a crystalline gold shell. Applied Surface Science 2014 ;Volum 316.(1) s. 171-178 http://dx.doi.org/10.1016/j.apsusc.2014.07.081

Paper 2: Singh, Gurvinder; Van Helvoort, Antonius; Bandyopadhyay, Sulalit; Volden, Sondre; Andreassen, Jens-Petter; Glomm, Wilhelm. Synthesis of Au nanowires with controlled morphological and structural characteristics. Applied Surface Science 2014 ;Volum 311. s. 780-788 http://dx.doi.org/10.1016/j.apsusc.2014.05.162

Paper 3: Bandyopadhyay, Sulalit; Andersen, Marte Kee; Awais, Muhammad; Sharma, Anuvansh; Raju, Rajesh; McDonagh, Birgitte Hjelmeland; Glomm, Wilhelm. Incorporation of Fe@Au nanoparticles into multiresponsive pNIPAM-AAc colloidal gels modulates drug uptake and release. Colloid and Polymer Science 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s00396-016-3944-1

Paper 4: Bandyopadhyay, S.; Singh, G.; Glomm, W.R.; Shape Control of gold nanostructures using binary surfactant mixtures. accepted in Materials Today Chemistry © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Paper 5: Bandyopadhyay, S.; Singh, G.; Sandvig, I.; Sandvig, A.; Glomm, W.R.; Makura-shaped gold nanostructures show high cytotoxicity in cancer cells - Is not included due to copyright

Paper 6: Bandyopadhyay, S.; Sharma, A.; Alvi, M.A.A.; Raju, R.; Glomm, W.R.; A robust method to calculate VPTT for hydrogels and hybrids - Is not included due to copyright

Paper 7: Bandyopadhyay, S.; Alvi, M.A.A.; Sharma, A.; Zhu, K.; Kjøniksen, A.L.; Nyström, B.; Glomm, W.R.; Influence of polymer coating on release of L-Dopa from Core-shell Fe@Au nanoparticle systems - Is not included due to copyright

Paper 8: Bandyopadhyay, S.; Sharma, A.; Glomm, W.R.; Influence of different shaped Gold nanoparticles functionalized with NIPAM based hydrogels on the release of Cytochrome - Is not included due to copyright
Publisher
NTNU
Series
Doctoral theses at NTNU;2016:294

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