Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for stimulus upon alternating magnetic field heating. Although more traditional methods, such as emulsion polymerization, have been used to realize these composite devices, the synthesis is problematic. Poisonous surfactants that are necessary to prevent agglomeration must be removed from the finished polymer, increasing the time and cost of the process. This study seeks to further explore non-toxic, biocompatible, non-residual, photochemical methods of creating stimuli responsive nanogels to advance the targeted biotherapeutic delivery field. Ultraviolet photopolymerization promises to be more efficient, while ensuring safety by using only biocompatible substances. The reactants selected for nanogel fabrication were N-isopropylacrylamide as monomer, methylene bisacrylamide as cross-linker, and Irgacure 2959 as ultraviolet photo-initiator. The superparamagnetic nanoparticles for encapsulation were approximately 10 nm in diameter and composed of magnetite to enable remote delivery and enhanced triggered release properties. Early investigations into the interactions of the polymer and nanoparticles employ a pioneering experimental setup, which allows for coincident turbidimetry and alternating magnetic field heating of an aqueous solution containing both materials. Herein, a low-cost, scalable, and rapid, custom ultraviolet photo-reactor with in-situ, spectroscopic monitoring system is used to observe the synthesis as the sample undergoes photopolymerization. This method also allows in-situ encapsulation of the magnetic nanoparticles simplifying the process. Size characterization of the resulting nanogels was performed by Transmission Electron Microscopy revealing size-tunable nanogel spheres between 50 and 800 nm by varying the ratio and concentration of the reactants. Nano-Tracking Analysis indicates that the nanogels exhibit minimal agglomeration as well as provides a temperature-dependent particle size distribution. Optical characterization utilized Fourier Transform Infrared and Ultraviolet Spectroscopy to confirm successful polymerization. When samples of the nanogels encapsulating magnetic nanoparticles were subjected to an alternating magnetic field a temperature increase was observed indicating that triggered release is possible. Furthermore, a model, based on linear response theory that innovatively utilizes size distribution data, is presented to explain alternating magnetic field heating results. The results presented here will advance targeted biotherapeutic delivery and have a wide range of applications in medical sciences like oncology, gene delivery, cardiology and endocrinology.

[ES] La presente tesis doctoral titulada "Nanodispositivos mesoporosos híbridos funcionalizados con enzimas para detección, liberación controlada y comunicación molecular" se centra en el diseño, preparación, caracterización y evaluación de distintos nanodispositivos híbridos orgánico-inorgánicos utilizando como soporte nanopartículas tipo Janus de oro y sílice mesoporosa, que se equipan con enzimas, especies fluorescentes y puertas moleculares. Como conclusión general, los estudios realizados muestran que la incorporación de enzimas sobre nanopartículas permite introducir funciones de reconocimiento con alta especificidad y diseñar nanodispositivos avanzados para distintas finalidades. La combinación de nanopartículas híbridas con grupos orgánicos como puertas moleculares, efectores enzimáticos y especies cromo- fluorogénicas o fármacos puede resultar muy versátil; y se espera que los resultados obtenidos puedan inspirar el desarrollo de nuevos materiales inteligentes con aplicación en distintas áreas como la nanomedicina y la detección de moléculas de interés. / [CAT] La present tesi doctoral titulada "Nanodispositius mesoporosos híbrids funcionalitzats amb enzims per a detecció, alliberació controlada i comunicació molecular" es centra en el disseny, preparació, caracterització i avaluació de distints nanodispositius híbrids orgànic-inorgànics utilitzant com a suport nanopartícules tipus Janus d'or i sílice mesoporosa, que s'equipen amb enzims, espècies fluorescents i portes moleculars. Com a conclusió general, els estudis realitzats mostren que la incorporació d'enzims sobre nanopartícules permeten introduir funcions de reconeixement amb alta especificitat i dissenyar nanodispositius avançats per a distintes finalitats. La combinació de nanopartícules híbrides amb grups orgànics com portes moleculars, efectors enzimàtics i espècies cromo-fluorogèniques o fàrmacs pot resultar molt versàtil; i s'espera que els resultats obsessos inspiren el desenvolupament de nous materials intel·ligents amb aplicació en distintes àrees com la nanomedicina i la detecció de molècules d'interés. / [EN] This PhD thesis entitled "Enzyme-functionalized hybrid mesoporous nanodevices for sensing, controlled release and molecular communication" is focused on the design, synthesis, characterization and evaluation of several hybrid organic-inorganic nanodevices using Janus gold-mesoporous silica nanoparticles as scaffolds, equipped with enzymes, fluorescent species and molecular gates. In conclusion, these studies show that the incorporation of enzymes on nanoparticles allows to introduce recognition capabilities with high specificity and to design advanced nanodevices for different purposes. The combination of hybrid nanoparticles with organic groups such as molecular gates, enzymatic effectors and chromo-fluorogenic species or drugs can be very versatile; and we hope that the obtained results inspire the development of new smart materials with application in different areas such as nanomedice and sensing. / Llopis Lorente, A. (2019). Enzyme-functionalized hybrid mesoporous nanodevices for sensing, controlled release and molecular communication [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/117612 / TESIS

A polymer brush is formed by densely grafting the chain ends of polymers onto a surface. This tethering of the long macromolecules has considerable influence on the surface properties, which can be additionally modified by changing the environmental conditions. In this context it is of special interest to understand and control the behavior of the grafted layer and to create surfaces that display a desired response to external stimulation. The present work studies densely grafted polymer brushes and the effects that such an environment imposes on an individual chain molecule in the grafted layer. For this purpose we developed a new self-consistent field approach to describe mixtures of heterogeneous chains comprised of differently sized hard spheres. Applying this method to the case of polymer brushes we consider a fraction of grafted molecules to be different from the majority brush chains. The modification of these chains includes a variation in the degree of polymerization, a different solvent selectivity behavior and a variable size of the free end-monomer. Due to the computational efficiency of the present approach, as compared for example to direct simulation methods, we can study the conformations of the modified 'guest' chains systematically in dependence of the relevant parameters. With respect to brush profile and the distribution of the free chain ends the new method shows very good quantitative agreement with corresponding simulation results. We also confirm the observation that these 'guest' chains can undergo a conformational transition depending on the type of modification and the solvent quality. For the cases studied in the present work we analyze the conditions to achieve a most sensitive behavior of this conformational switching. In addition, an analytical model is proposed to describe this effect. We compare its predictions to the numerical results and find good agreement.

Microfluidics is an expanding research field that lies at the interface of engineering, physics, chemistry and biology and offers promises in the development in a wide range of applications from point-of-care (POC) diagnostics to regenerative medicine, from drug testing to DNA sequencing. The number of publications in the field has been steadily growing in the last two decades and the trend does not show any sign of slowing down. On top of that, the market value generated by microfluidics is expected to quadruple in the time spam from 2013 to 2023: from 1.59 billion dollars in 2013, it is expected to grow to 8.64 billion dollars in 2023. There are however a series of limitations which prevent the full development of microfluidic technology. As it has already been pointed out in many publications in the last decade, the lack of a killer application capable of really making the difference out of the research labs and the academic playgrounds around the world is an impeding factor to the full-scale development of microfluidcs at an industrial level, also due to the lack of industrial standards. A number of authors, though, are of the opinion that the actual concept itself needs to challanged and that a complete re-thinking of the current technological platform should be done in order to make the breakthrough advance allowing a long-standing promising field to finally realise itself.In this work a completely new concept, based on volume-phase-transition smart-hydrogels, is presented and the foundations for a transistor-like technological platform are laid. A strong focus is therefore based on the basic element itself, i.e. volume-phase-transition smart-hydrogels, and on the possible ways that it might be integrated in microfluidic systems. Furthermore, basic circuits that lay the foundations for a logic system are presented together with other applications that replicate some elementary functions in microelectronics, such as oscillators. Finally, integration of logic gates as well as basic circuits is presented, in order to lay the foundations for chemical integrated microfluidic circuits.

Im Zusammenhang mit auf Reize reagierenden Materialien ist Licht aufgrund seiner hohen räumlichen und zeitlichen Auflösung von besonderer Bedeutung. Hierfür können molekulare Photoschalter, wie z.B. Azobenzole, in das Material eingebaut werden, um eine Reaktion auf Lichteinstrahlung von der molekularen auf die makroskopische Ebene zu übertragen. Fortschrittliche Moleküldesigns, wie z.B. Ortho-Fluorierung, führen dabei zu hervorragenden bistabilen Photoschaltern, die in Kombination mit Cyclodextrinen (CDs) als supramolekulare Bausteine eine Vielfalt an lichtempfindlichen Materialien ermöglichen. Um ein grundlegendes Verständnis der Wechselwirkungen von ortho-Fluorazobenzolen (FAzos) mit CDs zu erlangen, wurde in Kapitel II deren supramolekulare Wirt-Gast-Komplexierung untersucht. Hierbei konnte eine veränderte Barriere des Auffädelns der CDs beobachtet werden. Durch detaillierte Untersuchungen an polymeren Modellverbindungen in Kapitel III konnte gezeigt werden, dass das Auffädeln über die Z- im Vergleich zu den E-Isomeren der FAzos deutlich reduziert ist und dadurch die Bildung von Pseudo-Polyrotaxanen durch Bestrahlung mit Licht kontrolliert werden kann. Durch speziell konzipierte DOSY-Experimente konnte die Abfädelungskinetik aus Polyrotaxanen, bei denen die CDs durch das Z-Azobenzol auf der Achse fixiert wurden, verfolgt werden. Somit konnte gezeigt werden, dass eine Kontrolle der Bewegung von CDs durch Licht möglich ist. Auf Grundlage dieser Ergebnisse wurden in Kapitel IV neuartige lichtempfindliche Slide-Ring Materialien entwickelt, die bei Lichteinstrahlung eine reversible Änderung ihrer Steifigkeit aufweisen. Die Materialien wurden so konzipiert, dass sie ortho-Fluorazobenzole enthalten, die als durch Licht schaltbare Barrieren für das Gleiten von CDs entlang des Polymerrückgrats dienen. Hierdurch konnte eine reversible Änderung des Elastizitätsmoduls durch Bestrahlung mit Licht erzielt werden und somit ein erfolgreicher Konzeptnachweis erbracht werden. / In the context of stimuli-responsive materials, light is of particular importance due to its high spatial and temporal resolution. For this purpose, molecular photoswitches, such as azobenzenes, can be incorporated into the material to transfer a response to light irradiation from the molecular to the macroscopic level. Advanced molecular designs, such as ortho-fluorination, lead to excellent bistable photoswitches which, in combination with cyclodextrins (CDs) as supramolecular building blocks, enable a variety of light-responsive materials. To gain a fundamental understanding of the interactions of ortho-fluoroazobenzenes (FAzos) with CDs, their supramolecular host-guest complexation was investigated in Chapter II. An altered barrier for the threading of CDs was thereby observed. Detailed studies on polymeric model compounds in Chapter III showed that threading over the Z-isomers of the FAzos is significantly reduced compared to the E-isomers and that the formation of pseudo-polyrotaxanes can thus be controlled by irradiation with light. Using specially designed DOSY experiments, the threading kinetics from polyrotaxanes, in which the CDs where fixed on the axis by the Z-azobenzene, could be followed. This showed that it is possible to control the movement of CDs by light. Based on these results, novel photoresponsive slide-ring materials were developed in Chapter IV, which exhibit a reversible change in stiffness when exposed to light. The materials were designed to contain ortho-fluoroazobenzenes, which serve as photoswitchable barriers for the sliding of CDs along the polymer backbone. This enabled a reversible change of the elastic modulus to be accomplished by irradiation with light, thus providing a successful proof of concept.

In the realm of neuroelectronics, the challenge lies in achieving finer observations of physiological processes to comprehend neuronal interactions and computations. This necessitates the development of more compliant and biomimetic interfaces for improved integration with biological tissues, enabling finer physiological process observations. Commonly used flat and static electrode interfaces contrast sharply with the dynamic, complex, and three dimensional (3D) extracellular matrix (ECM) in which cells reside. Introducing 3D patterns on electrode surfaces enhances cell-chip coupling, improving the signal recording. Moreover, inorganic electrodes are stiff and rigid, creating mechanical mismatches with softer biological tissues, and they fail to fully capture ionic conduction.This thesis addresses these challenges by focusing on designing and engineering a multi-layer dynamic and stimuli-responsive bioelectronic interface. The system combines light-responsive, deformable polymers like Poly(Disperse Red 1-methacrylate) (pDR1m) with conductive polymers such as Poly(3,4-ethylenedioxythiophene): poly(stirensulfonate) (PEDOT:PSS). pDR1m responds to light, exhibiting 3D surface topography deformation, while PEDOT:PSS facilitates electrical recording and stimulation of cells, offering mixed electronic and ionic conduction as well as good mechanical properties. The potential use of an intermediate Polydimethylsiloxane (PDMS) film to improve layer adhesion is also explored. The individual and multi-layer samples were first optimized for spin coating manufacturing, and then thoroughly characterized to investigate their thickness, morphology, optical and electrochemical properties. Patterning of pDR1m-based samples was carried out using laser scanning confocal microscopy and a Lloyd’s mirror interferometer.The pDR1m\PEDOT:PSS sample demonstrates promising morphological and conductive properties, and the presence of PEDOT:PSS does not alter the absorption spectra of pDR1m. The multi-layer approach also supports efficient inscription of 3D surface reliefs without damaging the conductive layer. In conclusion, this work successfully designs conductive and dynamic light-driven films, which showcase good potential for bioelectronics and neuroelectronic interfaces. These interfaces could lead to enhanced investigations into combined electromechanical stimulation on cells and provide a more biomimetic coupling with biological tissues. / Inom neuroelektronikens område ligger utmaningen i att uppnå finare observationer av fysiologiska processer för att förstå neuronala interaktioner och beräkningar. Detta kräver utveckling av mer följsamma och biomimetiska gränssnitt för förbättrad integration med biologiska vävnader, vilket möjliggör finare fysiologiska processobservationer. Vanligt använda platta och statiska elektrodgränssnitt står i skarp kontrast till den dynamiska, komplexa och tredimensionella (3D) extracellulära matrisen (ECM) i vilken celler finns. Att introducera 3D-mönster på elektrodytor förbättrar cell-chip-kopplingen, vilket förbättrar signalinspelningen. Dessutom är oorganiska elektroder styva och stela, vilket skapar mekaniska felmatchningar med mjukare biologiska vävnader, och de lyckas inte helt fånga jonledning.Den här avhandlingen tar upp dessa utmaningar genom att fokusera på att designa och konstruera ett flerlagers dynamiskt och stimuli-responsivt bioelektroniskt gränssnitt. Systemet kombinerar ljuskänsliga, deformerbara polymerer som Poly(Disperse Red 1-methacrylate) (pDR1m) med ledande polymerer som Poly(3,4-etylendioxitiofen): poly(stirensulfonat) (PEDOT:PSS). pDR1m reagerar på ljus och uppvisar 3D-yttopografideformation, medan PEDOT:PSS underlättar elektrisk inspelning och stimulering av celler, erbjuder blandad elektronisk och jonledning samt goda mekaniska egenskaper. Den potentiella användningen av en mellanliggande polydimetylsiloxan (PDMS) film för att förbättra skiktvidhäftningen undersöks också. De individuella och flerskiktiga proverna optimerades först för spinnbeläggningstillverkning och karakteriserades sedan grundligt för att undersöka deras tjocklek, morfologi, optiska och elektrokemiska egenskaper. Mönster av pDR1m-baserade prover utfördes med laserskanning konfokalmikroskopi och en Lloyds spegelinterferometer.pDR1m\PEDOT:PSS-provet visar lovande morfologiska och ledande egenskaper, och närvaron av PEDOT:PSS förändrar inte absorptionsspektra för pDR1m. Flerskiktsmetoden stöder också effektiv inskription av 3D-ytreliefer utan att skada det ledande lagret. Sammanfattningsvis designar detta arbete framgångsrikt ledande och dynamiska ljusdrivna filmer, som visar upp god potential för bioelektronik och neuroelektroniska gränssnitt. Dessa gränssnitt kan leda till förbättrade undersökningar av kombinerad elektromekanisk stimulering på celler och ge en mer biomimetisk koppling med biologiska vävnader.

No description available.

Step-growth polymerization provided an effective method for the preparation of several high performance polymers. Step-growth polymerization was used for syntheses of poly(siloxane imides), polyesters, poly(triazole esters), poly(triazole ether esters), and epoxy networks. Each of these polymeric systems exhibited novel structures, and either photoreactive capabilities, or high performance properties. There is an increasing trend towards the development of photoactive adhesives. In particular these polymers are often used in flip bonding, lithography, stimuli responsive polymers, drug delivery, and reversible adhesives. The ability to tailor polymer properties carefully with exposure to light allows for very unique stimuli responsive properties for many applications. This dissertation primarily investigates photoreactive polymers for reversible adhesion for use in the fabrication of microelectronic devices. In particular cyclobutane diimide functionality within polyimides and poly(siloxane imides) and o-nitro benzyl ester functionality within polyesters acted effectively as chromophores to this end. Thermal solution imidization allowed for the effective synthesis of polyimides and poly(siloxane imides). 1,2,3,4-Cyclobutane tetracarboxylic dianhydride acted as the chromophore within the polymer backbone. The polyimides obtained exhibited dispersibility only in dipolar, aprotic, high boiling solvents such as DMAc or NMP. The obtained poly(siloxane imides) demonstrated enhanced dispersibility in lower boiling organic solvents such as THF and CHCl₃. Dynamic mechanical analysis and tensile testing effectively measure the mechanical properties of the photoactive poly(siloxane imides) and confirmed elastomeric properties. Atomic force microscopy confirmed microphase separation of the photoactive poly(siloxane imides). ¹H NMR spectroscopy confirmed formation of maleimide peaks upon exposure to narrow band UV light with a wavelength of 254 nm. This suggested photo-cleavage of the cyclobutane diimide units within the polymer backbone. Melt transesterification offered a facile method for the synthesis of o-nitro benzyl ester-containing polyesters. ¹H NMR spectroscopy confirmed the structures of the photoactive polyesters and size exclusion chromatography confirmed reasonable molecular weights and polydispersities of the obtained samples. ¹H NMR spectroscopy also demonstrated a decrease in the integration of the resonance corresponding to the o-nitro benzyl ester functionality relative to the photo-stable m-nitro benzyl ester functionality upon exposure to high-intensity UV light, suggesting photo-degradation of the adhesive. ASTM wedge testing verified a decrease in fracture energy of the adhesive upon UV exposure, comparable to the decrease in fracture energy of a commercial hot-melt adhesive upon an increase in temperature. Click chemistry was used to synthesize polyesters and segmented block copolyesters. Triazole-containing homopolyesters exhibited a marked increase (~40 °C) in Tg, relative to structurally analogous classical polyesters synthesized in the melt. However, the triazole-containing homopolyesters exhibited insignificant dispersibility in many organic solvents and melt-pressed films exhibited poor flexibility. Incorporation of azide-functionalized poly(propylene glycol) difunctional oligomers in the synthesis of triazole-containing polyesters resulted in segmented block copolyesters which exhibited enhanced dispersibility and film robustness relative to the triazole-containing homopolyesters. The segmented triazole-containing polyesters all demonstrated a soft segment Tg near -62 °C, indicating microphase separation. Dynamic mechanical analysis confirmed the presence of a rubbery plateau, with increasing plateau moduli as a function of hard segment content, as well as increasing flow temperatures as a function of hard segment content. Tensile testing revealed increasing tensile strength as a function of hard segment, approaching 10 MPa for the 50 wt % HS sample. Atomic force microscopy confirmed the presence of microphase separated domains, as well as semicrystalline domains. These results indicated the effectiveness of click chemistry towards the synthesis of polyesters and segmented block copolyesters. Click chemistry was also used for the synthesis of photoactive polyesters and segmented block polyesters. The preparation of 2-nitro-p-xylylene glycol bispropiolate allowed for the synthesis of triazole-containing polyesters, which exhibited poor dispersibility and flexibility of melt-pressed films. The synthesis of segmented photoactive polyesters afforded photoactive polyesters with improved dispersibility and film robustness. ¹H NMR spectroscopy confirmed the photodegradation of the o-nitro benzyl functional groups within the triazole-containing polyesters, which indicated the potential utility of these polyesters for reversible adhesion. Synthesis of the glycidyl ether of 2,2,4,4-tetramethyl-1,3-cyclobutane diol (CBDOGE) allowed for the subsequent preparation of epoxy networks which did not contain bisphenol-A or bisphenol-A derivatives. Preparation of analogous epoxy networks from the glycidyl ether of bisphenol-A (BPA-GE) provided a method for control experiments. Tensile testing demonstrated that, dependent on network Tg, the epoxy networks prepared from CBDOGE exhibited similar Young's moduli and tensile strain at break as epoxy networks prepared from BPAGE. Dynamic mechanical analysis demonstrated similar glassy moduli for the epoxy networks, regardless of the glycidyl ether utilized. Tg and rubbery plateau moduli varied as a function of diamine molecular weight. Melt rheology demonstrated a gel time of 150 minutes for the preparation of epoxy networks from CBDO-GE and 78 minutes for the preparation of epoxy networks from BPA-GE, with the difference attributed to increased sterics surrounding CBDO-GE. These results indicated the suitability of CBDO-GE as a replacement for BPA-GE in many applications. / Ph. D.

The present thesis focuses on the fabrication of bio-stimuli responsive micro- and nano-carriers for drug delivery applications. In particular, the objective of this work is to investigate the possibility of using polypeptide drug protamine and glycosaminoglycan drug, chondroitin sulphate as stimuli responsive components in the design of bioresponsive carriers. These biopolymers are biocompatible, biodegradable and clinically used for various applications. Two designs that incorporate these stimuli responsive components have been studied in this thesis. The first design involves hollow micro and nanocapsules that have been fabricated by incorporating the stimuli responsive biopolymers as wall components. Upon exposure to biological triggers, these hollow capsules disintegrate releasing the encapsulated drug. The second design consists of mesoporous silica nanoparticles-biopolymer hybrids. The mesoporous silica nanoparticles act as a gated scaffold that carries the drug molecules. The mesopores of these drug loaded nanoparticles are then blocked with the bioresponsive polymers. Upon exposure to the bio-triggers which consist of enzymes over-expressed in conditions such as cancer and inflammation, these “molecular gates” disintegrate allowing the drug trapped in the mesoporous silica nanoparticles to escape into the surroundings. The thesis has been divided into five chapters: Chapter 1 is an introduction to bio-responsive drug delivery. The broad classification of stimuli used in responsive drug delivery systems are visited. A brief discussion on the various types of bio-stimuli that can be utilized in designing bio-responsive systems is also included in this chapter. Chapter 2 defines the aims and scope of the thesis which is followed by an overview of the various design parameters involved in the fabrication of systems presented in this work. The major stimuli responsive components and the architectures incorporating these elements are discussed in detail here. A literature review of the various carrier designs involved in the study is provided , with special emphasis on stimuli responsive drug delivery. Chapter 3 gives an overview of the various materials and methods involved in this work. A summary of the various characterisation techniques used in the thesis is also included along with the details of the experiments that has been carried out. Chapter 4 provides an overview of the results and discussions of the thesis. The chapter has been divided into six sections: Chapter 4.1 deals with the fabrication of a hollow microcapsule system incorporated with protamine as the stimuli responsive element for bio-responsive drug delivery. The hollow microcapsules that were fabricated by Layer by Layer assembly of protamine and heparin display pH responsive variations in permeability and disintegrate in the presence of the enzyme trypsin that degrades protamine. The biologically triggered enzyme responsive drug release from these microcapsules is also demonstrated using enzymes secreted by colorectal cancer cells. Chapter 4.2 presents nanocapsules fabricated from protamine and heparin. The pH and enzyme responsive drug release of this systems is evaluated in vitro. A wall crosslinking strategy has been tested to control the rate of drug release under physiological pH conditions in the absence of the trigger. The cellular interactions of these nanocapsules loaded with an anticancer drug, doxorubicin was studied using cancer cell lines. Bioavailability studies of doxorubicin encapsulated in these nanocapsules were performed using a BALB/c mice model. Chapter 4.3 discusses the fabrication of a hollow microcapsule system that can disintegrate in response to dual biological stimuli. These carriers have been fabricated by incorporating protamine and chondroitin sulphate as the wall components. Due to the incorporation of two separate stimuli responsive components in the walls, these capsules are expected to be sensitive to the enzymes trypsin or hyaluronidase I. Chapter 4.4 deals with the fabrication of dual enzyme responsive hollow nanocapsule which can be targeted to deliver anticancer agents specifically inside cancer cells. The enzyme responsive elements integrated in the hollow nanocapsule walls can undergo degradation in presence of either of the enzymes trypsin or hyaluronidase I leading to the release of encapsulated drug molecules. The drug release from these nanocapsules which were crosslinked and functionalised with folic acid, is evaluated under varying conditions. The cellular uptake and intracellular drug delivery by these nanocapsules were evaluated in cervical cancer cell lines. Chapter 4.5 introduces a mesoporous silica nanoparticle − protamine hybrid system. The system consists of a mesoporous silica nanoparticle support whose mesopores are capped with protamine which effectively blocks the outward diffusion of the drug molecules from the mesopores of the mesoporous silica nanoparticles. Upon exposure to the enzyme trigger, the protamine cap disintegrates opening up the molecular gates and releasing the entrapped drug molecules. The drug release from this system is evaluated in different release conditions in the presence and absence of the enzyme trigger. The ability of these particles to deliver hydrophobic anticancer drugs and induce cell death in colorectal cancer cells has also been demonstrated. Chapter 4.6 discusses the fabrication of another mesoporous silica nanoparticles based bio-responsive drug delivery system consisting of mesoporous silica and chondroitin sulphate hybrid nanoparticles. The ability of the system to modulate drug release in response to hyaluronidase I is demonstrated. By utilizing a cervical cancer cell line, we have demonstrated the cellular uptake and intracellular delivery of hydrophobic drugs encapsulated in these particles. Interestingly, the system showed ability to enhance the anticancer activity of hydrophobic drug curcumin in these cancer cells. Chapter 5 gives a summary of the general conclusions drawn from the thesis work.

Janus particles, named after the two faced Roman god Janus, possess unique asymmetry and combine two distinct functions at their opposite sides, allowing them to target complex self-assembled architectures and materials inaccessible for homogeneous building blocks. In this study, three areas regarding the topic of Janus particles were explored: the synthesis of Janus particles, their (self-) assembly, and applications. In the first part of the work, we have drawn our attention to the optimization of the synthetic procedures concerning the preparation of Janus particles and to the extending of the current Janus particle library by adding new geometries to the list. In the case of spherical Janus particles, we have developed an easy approach to tailor the Janus ratio of the resulting particles, thus, extending the possibilities of the Pickering emulsion approach for the creation of a variety of Janus particle architectures. Additionally, a new methodology was employed to measure directly and in situ the position/contact angle of the prepared Janus particles with different Janus ratios at a water-oil interface. It was further concluded that having simply two different functionalities on a particle surface does not necessarily imply amphiphilic behavior: only in the case of large wettability contrasts our particles were in a true Janus regime. In the case of platelet-like Janus particles, we have developed a completely new approach for their large-scale synthesis, which involved a reduced number of steps compared to the spherical Janus particles. In the second part of the work, the assembly behavior of various kinds of functional spherical Janus particles was investigated depending on the nature of the Janus particles and the surrounding media conditions. Oppositely charged, uncharged amphiphilic, and charged amphiphilic Janus particles were fabricated comprising different responsive polymers on their surface, and their assembly was investigated depending on the pH value of the dispersion, the ionic strength, or the solvent. It was found that, under specific conditions, the Janus particles formed hierarchical chain-like structures in solutions, which were not observed in the case of the homogeneous particle mixtures. The obtained results indicate that the fundamental understanding of the Janus particle assembly mechanisms is crucial for the programmed formation of desired structures. In the third part of the work, we have focused on the applications of our developed hybrid hairy Janus particles and proposed two main directions that would benefit from the unique properties or architecture of the Janus particles. The first direction is based on the exploitation of the superior interfacial activity of the Janus particles and their use for interfacial catalysis. The second proposed direction for the application of Janus particles is based on their use as building blocks for functional structured surfaces. The prepared surfaces were thoroughly characterized and tested for their performance toward anti-icing as well as anti-fouling applications. Ultimately, the developed functional surfaces based on Janus particles as building blocks are very promising for their future application in the coating technology.