In this thesis, glucose responsive hydrogels based on cross-linked dextran molecules were studied to determine the diffusion rate of an insulin analogue. Investigations of the interaction between concanavalin A and dextran, both in free solution and in the form of glucose responsive hydrogels were conducted. The free solution results have shown that there is an increase of association constant between concanavalin A and dextran when the molecular mass of the dextran is increased. Free solution viscometric tests have shown that increasing the molecular mass or the concentration of the dextran increases the viscosity. The hydrogels have been shown to form for dextrans of molecular mass 43kD or greater. Experiments conducted with hydrogel membranes in a diffusion cell have shown that the batch to batch reproducibility of hydrogel transport properties is low. However, clear evidence of glucose enhanced transport was obtained and these results were compared with predictions obtained from a theoretical model of gel permeability that accounts for competitive displacement of affinity cross links. Oscillatory rheological tests of gelation mixtures which showed an increase in complex viscosity at the gel point with increasing molecular mass of dextran were in agreement with empirical observations that gels formed from the highest molecular mass dextrans were more physically robust and easier to handle. Swelling rate experiments have shown that the rate of hydration of a hydrogel in the presence of glucose is decreased due to the osmotic pressure of the glucose. This work has shown that the multivalent nature of concanavalin A may not be a necessary pre-requisite for this type of hydrogel due to spatial constraints decreasing the number of potential affinity bonds per tetramer. In-house production of more tightly defined dextrans might be expected to reduce heterogeneity and improve the reproducibility of this type of hydrogel membrane.

The field of biomaterials has seen huge development over the past decade with enormous efforts invested in discovering materials with improved biocompatibility, application and versatility. Polymers can display many properties that make them ideal biomaterials, such as their potential flexibility, low weight, low cost and biodegradability. Moreover, they can be prepared in a wide variety of compositions and forms and be readily fabricated into various shapes and structures. Polymer microarrays represent an efficient high-throughput platform for the screening and discovery of new materials compared to conventional assays with advantages such as high-density screening, internal consistency of assays and the requirement for only small quantities of material. The first part of this thesis describes work in the area of diabetes research with a focus on how dysfunctional β-cells could be replaced by the transplantation of β-cells obtained from pluripotent stem cells. To achieve this aim, high numbers of β-cells are required. A polymer microarray screening approach was used to identify a number of polymers that promoted the attachment of pancreatic progenitor cells and enhanced cell proliferation. Multiple scale-up fabrication techniques were assessed to establish the most suitable approach and surface for long term cell culture leading to the obtainment of reproducible in situ polymerised polymer layers with enhanced binding properties toward pancreatic progenitor cells. These surfaces have the potential to support cell adhesion and proliferation and could find potential use in the industrial sector to increase the production of pancreatic progenitor cells in vitro. In the second part, efforts were made to gain a better understanding of the maturation of β-cells and their behaviour, with the development of 3D hydrogels based on the previously identified polymers. In this scenario, parameters such as stiffness and porosity were evaluated to identify the best environmental conditions to support 3D cell culturing of pancreatic progenitor cells. Several approaches were tested to generate scaffolds with suitable stiffness and porosity leading to the obtainment of scaffolds based on the previously identified polymer composition and with controlled porosity and stiffness. These scaffolds could represent a suitable environment to allow a better understanding of cell organisation and regulation. In a third avenue of work, arrays of 3D biocompatible materials, which were tailored for varying elasticity, hardness, and porosity (to provide the necessary physical cues to control cellular functions) were fabricated. In this chapter, details of the development of an array of eighty 3D double-network hydrogel features are reported. The array features can be produced as single or double networks and modulated in terms of stiffness, viscoelasticity and porosity to assess cell response to materials with a wide range of properties. The final part of the thesis describes the development and screening of polymeric materials to allow a better understanding of cell–surface interactions with various cell types. To investigate the correlation between cell attachment and the nature of the polymer, a series of random and block copolymers were synthesised and examined for their abilities to attach and support the growth of human cervical cancer cells (HeLa) and human embryonic kidney cells (HEK293T), with attachment modelled on monomer ratios, arrangement, and polymer chain length. The results of this screening showed differences between block copolymers and random copolymers in cell adhesion and provide interesting insight into the improvement of polymer coatings for cell culture.

Bio-nanotechnology is the use of biomolecules to control both the structure and property of nanomaterials. No biomolecule has been employed more often than DNA as exemplified in the numerous demonstrations of DNA-directed assembly of nanomaterials. DNA has been used to covalently functionalize and assemble soft nanoparticles (e.g. liposomes) and hard nanoparticles (e.g. gold and silica nanoparticles) into a variety of hierarchical nanostructures. The majority of previous work however has focused on the latter, i.e., the assembly of “hard” nanoparticles such as gold nanoparticles (AuNPs) as oppose to the assembly of soft materials. The primary focus of this thesis is to add to the growing field of DNA-directed assembly of soft materials owing to the promise of such materials in a variety of analytical and biomedical applications. The first class of soft materials considered are liposomes which interestingly can be deformed by relatively weak intermolecular forces. In addition, DNA anchored to its surface can readily diffuse laterally within the lipid bilayer while DNA attached to inorganic nanoparticles remain fixed in position. We systematically consider the effect of varying the liposome structure, size, charge, and fluidity on liposome assemblies, in chapter 2. In addition, the interesting properties of liposomes are highlighted by a side-by-side comparison to DNA-functionalized gold nanoparticles, offering fundamental insights into DNA-directed assembly. Furthermore, hybrid DNA-directed assemblies composed of both AuNPs and liposomes are described in Chapter 3. In particular, the photothermal effects of such DNA-coupled liposome and AuNP assemblies were modulated by controlling the distance between liposome and AuNP allowing such systems to have potential application in drug-delivery. In chapter 4, the utility of liposomes is demonstrated as we exploit the fluidity of its diffuse bilayer with split aptamer functionalization for the rapid and selective detection of metabolites. The second class of soft material of interest in this thesis are hydrogels, which are cross-linked hydrophilic polymers. Because hydrogels are swollen in water, they can be used to immobilize biomolecules such as DNA for a myriad of applications. In chapter 5, the preparation and characterization of DNA-functionalized polyacrylamide hydrogels are presented. The use of such a DNA-modified hydrogel for the simultaneous detection and removal of mercury from water is subsequently demonstrated.

PVA hydrogels are potential biomaterials for various tissue-engineering applications. PVA hydrogels are relevant to vascular graft development due to their excellent biocompatibility and the capability to possess a wide range of mechanical properties based on compositional and processing parameters. This thesis aims to characterize some PVA hydrogels mechanically, biologically, and physically. A constitutive formulation is used for mechanical characterization, which allows for analysis of any possible stress-strain configuration applied to the material. A bovine aortic endothelial cell adhesion study under physiologic blood flow conditions comprises the biologic characterization, which gives insight into how human endothelial cells might interact with PVA hydrogels in a vascular graft application. A high-resolution SEM study is used to physically characterize the material, which furthers the understanding of the reactions of this material in vivo. These characterizations of PVA hydrogels will aid in the development of tissue-engineered products, in particular, the potential use as a vascular grafting biomaterial.

Είναι γνωστό ότι τα λιποσώματα παρέχουν πολλά πλεονεκτήματα για τη χορήγηση και /ή τη στόχευση φαρμάκων (Lasic 1993, Gregoriadis 1988). Κατά τη χορήγηση λιποσωμικών φαρμακομορφών για τοπική (topical) εφαρμογή ή εφαρμογή σε επιθήλια (mucosal) (Rollan 1993, Schreier and Bouwstra 1994) είναι απαραίτητο οι ρεολογικές και βλεννοσυγκολητικές ιδιότητες των λιποσωμικών διασπορών να ρυθμίζονται ανάλογα με την επιδιωκόμενη οδό χορήγησης. Αυτό μπορεί εύκολα να επιτευχθεί με τη προσθήκη παραγόντων αύξησης ιξώδους (gelling agents) στις λιποσωμικές διασπορές. Συνεπώς προκύπτουν σύνθετες φαρμακοτεχνικές μορφές που από δομικής σύστασης είναι διασπορές λιποσωμικών μορφών φάρμακων σε συστήματα γελών (drug-in-liposome-in-gel). Ανάλογα με το βαθμό συγκράτησης του φαρμάκου στα λιποσώματα μετά τη διασπορά των λιποσωμάτων στην επιθυμητή φαρμακοτεχνική μορφή, μπορεί να τροποποιηθεί και ο ρυθμός απελευθέρωσης του φαρμάκου από τέτοια συστήματα. Αυτό συνδέεται σε μεγάλο βαθμό κυρίως με δύο ομάδες παραγόντων: • Πρώτον με τη σταθερότητα των λιποσωμάτων (ακεραιότητα μεμβράνης και μηχανική σταθερότητα) κατά τη διασπορά σε ημι-στερεές φαρμακοτεχνικές μορφές, κάτι το οποίο συνδέεται τόσο με την σκληρότητα (rigidity) της μεμβράνης του λιποσωμικού φορέα όσο και με τις φυσικές ιδιότητες του ημι-στερεού συστήματος (ιξώδες και ρεολογικές ιδιότητες). • Δεύτερον, με τις φυσικοχημικές ιδιότητες του προς μορφοποίηση φάρμακου. Όσο πιο λιπόφιλο είναι ένα φάρμακο και όσο μικρότερη η διαλυτότητα του στο νερό, τόσο μεγαλύτερος θα είναι λογικά ο χρόνος συγκράτησης του στις λιπιδικές διπλοστοιβάδες των λιποσωμάτων συγκριτικά με αμφίφιλα φάρμακα που έχουν σημαντικά υψηλότερη διαλυτότητα στο νερό. Επειδή σε ανάλογα σύνθετα (φάρμακο-σε-λιπόσωμα-σε-γέλες) συστήματα χορήγησης είναι πιθανόν να πρέπει να συνυπάρχουν εκτός από τον παράγοντα αύξησης του ιξώδους και άλλα έκδοχα, κυρίως παράγοντες που αυξάνουν τη διαλυτότητα διάφορων ουσιών ή επιφανειοδραστικά, ο σκοπός της παρούσας μελέτης ήταν η εξέταση της επίδρασης τέτοιων εκδοχών κατά την προσθήκη τους στα παραπάνω συστήματα. Πιο συγκεκριμένα μελετήθηκε η επίδραση των εξής εκδόχων: Transcutol, Propylene-glycol, Cremophor και Labrafac στη σταθερότητα λιποσωμικών μορφών φαρμάκων και στο ρυθμό απελευθέρωσης υδρόφιλων και λιπόφιλων μορίων από συστήματα διασποράς λιποσωμικών μορφών τέτοιων ουσιών σε γέλες (drug-in-liposome-in-gel). Τα έκδοχα αυτά μόνα ή σε συνδυασμό μεταξύ τους καθως και σε συνδυασμό με άλλους φορείς προσφέρονται για την παρασκευή κατάλληλων φαρμακοτεχνικών μορφών που αποβλέπουν στην αύξηση διαλυτότητας, απορρόφησης και τελικά της βιοδιαθεσιμότητας δυσδιάλυτων φαρμάκων Για την εκτίμηση του βαθμού επίδρασης των πιο πάνω αναφερθέντων εκδοχών στη σταθερότητα λιποσωμικών μορφών φαρμάκων και στο ρυθμό απελευθέρωσης τόσο των υδρόφιλων όσο και λιπόφιλων φάρμακων από συστήματα διασποράς λιποσωμικών μορφών τους σε γέλες (drug-in-liposome-in-gel). χρησιμοποιήθηκε ως μοντέλο υδρόφιλων μορίων η καλσεΐνη ενώ ως μοντέλο υδρόφοβων ουσιών η γκριζεοφουλβίνη. Εδώ ως παράγοντες αύξησης του ιξώδους για την παρασκευή των σύνθετων φαρμακευτικών μορφών, φάρμακο-σε-λιπόσωμα-σε-γέλες χρησιμοποιήθηκαν: (Ι) το πολυμερές του ακρυλικού οξέος, carbopol 974PNF, (ΙΙ) το πολυμερές υδροξυ-αιθυλ-κυτταρίνης (HEC-Hydroxyethylcellulose) καθως και (ΙΙΙ) μίγμα των δυο πολυμερών. Γενικά από τη μελέτη αυτή συμπεραίνουμε ότι: Η επίδραση των προς εξέταση παραγόντων στη σταθερότητα των λιποσωμάτων εξαρτάται από: τη λιπιδική σύσταση, την προσθήκη χοληστερόλης κατά την παρασκευή των λιποσωμάτων, τη λιποφιλικότητα του εκδόχου και τη συγκέντρωσή του. Σχετικά με τη σταθερότητα των λιποσωμάτων παρουσία των εκδόχων που μελετήθηκαν: 1. Tα PC λιποσώματα σπάνε πολύ εύκολα με και χωρίς την παρουσία των εκδοχών στο φορέα υδρογέλης. 2. Τα πιο ανθεκτικά λιποσώματα DSPC/Chol 1:1 φαίνεται να έχουν μεγαλύτερη σταθερότητα. Όμως και στις δυο περιπτώσεις (PC και DSPC/Chol) η σταθερότητα των λιποσωμάτων στους παράγοντες αυτούς μειώνεται ακολουθώντας την εξής σειρά: Transcutol ≈ Propylene-glycol < Cremophor < Labrafac. 3. To Labrafac διαταράσσει στο μεγαλύτερο βαθμό τις λιπιδικές διπλοστοιβάδες προκαλώντας τη μεγαλύτερη διαρροή των εγκλωβισμένων μορίων προκαλώντας σημαντικές δομικές μεταβολές στα λιποσώματα. 4. H χοληστερόλη αυξάνει την σταθερότητα των λιποσωμάτων κυρίως παρουσία των εκδοχών με μια σχετική ασθενή δράση αλλά όχι σημαντικά παρουσία του εκδόχου Labrafac. Σχετικά με τη κινητική απελευθέρωσης ουσιών από λιποσωμικές τους μορφές που διασπείρονται σε γέλες παρουσία των εκδόχων που μελετήθηκαν: 1. Ένα σημαντικό εύρημα είναι ότι υπάρχει μεγάλη διαφορά στη συμπεριφορά απελευθέρωσης λιπόφιλων και υδρόφιλων μορίων από λιποσωμικές μορφές τους όταν τα τελευταία διασπείρονται σε συστήματα υδρογέλων παρουσία και απουσία των εκδόχων καθως και στη μεταξύ τους απελευθέρωση. 2. Σε γενικές γραμμές η απελευθέρωση των εγκλωβισμένων στα λιποσώματα ουσιών, όταν αυτά διασπείρονται στις γέλες που περιέχουν έκδοχα, φαίνεται να συνδέεται-επηρεάζεται από τη σταθερότητα των λιποσωμάτων παρουσία αυτών των εκδόχων, όπως ευρέθηκε στο πρώτο μέρος της μελέτης. Η κινητική απελευθέρωσης λιπόφιλων φαρμάκων από σύνθετα συστήματα όπως αυτά που μελετήθηκαν μπορεί να επιβραδύνεται σημαντικά όταν μέσα στις μορφές προστίθενται έκδοχα με υψηλή λιπόφιλα (Labrafac- γκριζεοφουλβίνη) (πιθανή κατανομή της γκριζεοφουλβίνης σε λιπόφιλες περιοχές). Κλείνοντας επισημαίνουμε ότι η ανακάλυψη νέων συστημάτων χορήγησης φαρμάκων αποτελεί σήμερα τη μεγαλύτερη πρόκληση για τους επιστήμονες. Οι πιο πάνω φορείς συγκαταλέγονται ανάμεσα στα πιο σπουδαία συστήματα χορήγησης φαρμάκων όχι μόνο λόγω συμβατότητας τους ως προς το ανθρώπινο οργανισμό αλλά και εξαιτίας της μεγάλης δυνατότητας εφαρμογών που προσφέρουν. Απώτερος σκοπός αυτής της μελέτης είναι η καταχώρηση στη βιβλιογραφία νέων στοιχείων σχετικά με την επίδραση αυτών των εκδοχών και συνεπώς η διευκόλυνση κατά την επιλογή των καταλληλότερων συνδυασμών φορέων-εκδοχών στο σχεδιασμό επιθυμητών φαρμακοτεχνικών μορφών. / It is well known that liposomes offer many advantages for the delivery and/or targeting of drugs (Lasic 1993, Gregoriadis 1988). When mucosal or topical delivery of liposomal formulations is considered (Rollan 1993, Schreier and Bouwstra, 1994), it is essential that rheological and/or mucoadhesive properties of the liposome dispersions are adjusted accordingly, depending on the intended route of administration. This can be easily dome by adding gelling agents in the liposomal dispersions. Thereby, eventually a drug-in-liposome-in gel complex formulation is developed. Depending on the retention of the drug in the liposomes after the liposomes are dispersed in the preferred formulation, the release rate of the drug may be modified. This is highly related with two major groups of factors; • First the stability of the liposomes (membrane integrity and mechanical stability) during dispersion in the semi-solid formulation that may be related to the vesicle-membrane rigidity as well as the semisolid system physical properties (viscosity and rheological properties). • Second, the physicochemical properties of the drug formulated. A more lipophilic drug with low aqueous solubility should be logically retained for longer time periods in liposome lipid bilayers when compared with amphiphillic drugs with considerable high aqueous solubility (that will be the driving force to move drug molecules to partition in the aqueous environments until saturation occurs). In some cases, in addition to the gelling agents it is essential to have also other excipients in the complex drug-in-liposome-in-gel systems, as solubilizers, surfactants, co-surfactants et.c. Herein, we evaluate the effect of such excipients on the release of drugs from complex systems. We chose to use trancutol, propylene glycol, cremophor and labrafac-hydro, that are commonly used excipients in pharmaceutical formulations. In order to evaluate the extent to which these compounds can affect the release rate of drugs from drug-in-liposome-in-gel systems we followed the release of two model compounds, one hydrophilic dye (calcein) and one lipophilic drug (griseofulvin). The effect of the rigidity of liposomal membranes was evaluated by testing two different liposome lipid compositions for each case of encapsulated compounds, one that is known to be what is called “leaky”, which is the plain PC (egg lecithin) composition, and one which is very rigid, which is the DSPC/Chol (1:1 mol/mol) composition. Additionally, we also evaluated the effect of the gel composition and characteristics, by studying the release of both drugs from liposomes that have been dispersed in systems with different properties. For this we used gels composed of the acrylic acid based polymer Carbopol 974, which is a substance of many commercially available semisolid formulations, at two different concentrations (same rheological properties and different viscosity) as well as a cellulose based gel, composed of hydroxyethyl-cellulose (different rheological properties). Additionally we evaluated also a mixture of the two polymers, which has been proposed as a formulation base with several advantages, for vaginal delivery of drugs. In addition, we studied the stability of liposomes during incubation in the presence of the plain excipients (in 2 different concentrations, 10% and 25%) in order to see if this can be correlated on the effect of the same agents on drug release from the complex systems. The general conclusion extracted from the experimental results of this study is that the effect of the excipients on liposome stability depend on (i) the lipid composition of the liposomal membranes, (ii) the inclusion of cholesterol in the liposomes or not, (iii) the lipophilicity of the excipient and (iv) the concentration of the excipient. More analytically: In respect to liposome stability: 1. PC liposomes are easily disrupted with or without the presence of the excipients in the gels. 2. The very rigid DSPC/Chol (1:1 mol/mol) liposomes demonstrate higher stability. 3. In both cases the effect of the excipients follows the sequence: Transcutol ≈ Propylene-glycol < Cremophor < Labrafac. 4. Labrafac has the highest effect on liposome stability it practically dissolves liposomal membranes. 5. Cholesterol inclusion in liposomal membranes results in increased stability, however even the most stable DSPC/Chol (1:1) liposomes are very unstable in presence of Labrafac. In respect to the release of liposomal drugs from the complex systems in presence of the excipients studied: 3. A significant finding is that there is a difference in the release pattern and rate between lipophilic and hydrophilic liposome-encapsulated molecules, in the presence of excipient or not (control studies).. 4. In general, there seems to be a correlation between the stability of liposomes in presence of excipients and the effect that the specific excipient has on the release kinetics of liposome encapsulated molecules from complex drug-in-liposome-in-gel systems. 5. The release of lipophilic molecules (that are encapsulated in the lipospmes) from complex systems can be substantially sustained when lipophilic excipients are added in the gel (as is the case of griseofulvin and labrafac). Concluding, we stress the fact that the invention of new drug delivery systems with better performance is a great challenge for scientists involved in pharmaceutics. The systems studied here are offering many advantages due to their biocompatible nature and the extended number of applications they may have. The final scope of this study is the entry of new data about the effect of excipients on the properties of complex drug delivery systems. As the availability similar data in the related literature increases, it will become more easy to make the best selection of excipients during the development of better formulations for existing of new drugs.

We present a platform that allows homogeneous and heterogeneous 3-D soft materials to be continuously defined in a single step. Biopolymer solutions are introduced to a microfluidic device and radially distributed to feed to a common outlet at the device center. This forms concentric sheaths of complex fluids and upon crosslinking, a hydrogel tube at the exit. This approach allows for the controlled and continuous extrusion of tubes with tailored diameters of 500 μm to 1500 μm, wall thicknesses of 20 μm to 120 μm, and compositions, as well as predictable mechanical and chemical properties. Using the same platform, single and multi-walled hydrogel tubes with defined heterogeneities and patterns of discrete spots of secondary biopolymer materials can be continuously extruded. A tube-hosting device is presented which can independently perfuse and superfuse isolated tube segments, allowing precise microenvironmental control without cannulation for up to an hour.

We present a platform that allows homogeneous and heterogeneous 3-D soft materials to be continuously defined in a single step. Biopolymer solutions are introduced to a microfluidic device and radially distributed to feed to a common outlet at the device center. This forms concentric sheaths of complex fluids and upon crosslinking, a hydrogel tube at the exit. This approach allows for the controlled and continuous extrusion of tubes with tailored diameters of 500 μm to 1500 μm, wall thicknesses of 20 μm to 120 μm, and compositions, as well as predictable mechanical and chemical properties. Using the same platform, single and multi-walled hydrogel tubes with defined heterogeneities and patterns of discrete spots of secondary biopolymer materials can be continuously extruded. A tube-hosting device is presented which can independently perfuse and superfuse isolated tube segments, allowing precise microenvironmental control without cannulation for up to an hour.

This thesis includes two parts related to hydrogels as therapeutically useful constructs: a biomimetic hydrogel carrying stem cells for bone regeneration and an acid-sensitive hydrogel carrying drugs for cancer therapy. In tissue engineering, one of the biggest difficulties is the control of stem cell fate on scaffolds. A biodegradable and cell attachable cross-linker was synthesized by one-step Michael additional reaction, and was used to fabricate a novel hydrogel to control the stem cell fate. For anti-cancer therapy, releasing drug on tumor cells or organs while having low effects on health cells under physiological conditions is a critical requirement. Two nature polymers are modified to achieve loading anti-cancer drug while forming hydrogels which can selectively release the drug in tumor environment by acid-sensitive linkages.

This thesis includes two parts related to hydrogels as therapeutically useful constructs: a biomimetic hydrogel carrying stem cells for bone regeneration and an acid-sensitive hydrogel carrying drugs for cancer therapy. In tissue engineering, one of the biggest difficulties is the control of stem cell fate on scaffolds. A biodegradable and cell attachable cross-linker was synthesized by one-step Michael additional reaction, and was used to fabricate a novel hydrogel to control the stem cell fate. For anti-cancer therapy, releasing drug on tumor cells or organs while having low effects on health cells under physiological conditions is a critical requirement. Two nature polymers are modified to achieve loading anti-cancer drug while forming hydrogels which can selectively release the drug in tumor environment by acid-sensitive linkages.

Bio-nanotechnology is the use of biomolecules to control both the structure and property of nanomaterials. No biomolecule has been employed more often than DNA as exemplified in the numerous demonstrations of DNA-directed assembly of nanomaterials. DNA has been used to covalently functionalize and assemble soft nanoparticles (e.g. liposomes) and hard nanoparticles (e.g. gold and silica nanoparticles) into a variety of hierarchical nanostructures. The majority of previous work however has focused on the latter, i.e., the assembly of “hard” nanoparticles such as gold nanoparticles (AuNPs) as oppose to the assembly of soft materials. The primary focus of this thesis is to add to the growing field of DNA-directed assembly of soft materials owing to the promise of such materials in a variety of analytical and biomedical applications. The first class of soft materials considered are liposomes which interestingly can be deformed by relatively weak intermolecular forces. In addition, DNA anchored to its surface can readily diffuse laterally within the lipid bilayer while DNA attached to inorganic nanoparticles remain fixed in position. We systematically consider the effect of varying the liposome structure, size, charge, and fluidity on liposome assemblies, in chapter 2. In addition, the interesting properties of liposomes are highlighted by a side-by-side comparison to DNA-functionalized gold nanoparticles, offering fundamental insights into DNA-directed assembly. Furthermore, hybrid DNA-directed assemblies composed of both AuNPs and liposomes are described in Chapter 3. In particular, the photothermal effects of such DNA-coupled liposome and AuNP assemblies were modulated by controlling the distance between liposome and AuNP allowing such systems to have potential application in drug-delivery. In chapter 4, the utility of liposomes is demonstrated as we exploit the fluidity of its diffuse bilayer with split aptamer functionalization for the rapid and selective detection of metabolites. The second class of soft material of interest in this thesis are hydrogels, which are cross-linked hydrophilic polymers. Because hydrogels are swollen in water, they can be used to immobilize biomolecules such as DNA for a myriad of applications. In chapter 5, the preparation and characterization of DNA-functionalized polyacrylamide hydrogels are presented. The use of such a DNA-modified hydrogel for the simultaneous detection and removal of mercury from water is subsequently demonstrated.