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

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.