Showing papers by "Frank Caruso published in 2011"
TL;DR: The experiments reported here demonstrate the viability of controlled single spin probes for nanomagnetometry in biological systems, opening up a host of new possibilities for quantum-based imaging in the life sciences.
Abstract: Fluorescent particles are routinely used to probe biological processes1. The quantum properties of single spins within fluorescent particles have been explored in the field of nanoscale magnetometry2,3,4,5,6,7,8, but not yet in biological environments. Here, we demonstrate optically detected magnetic resonance of individual fluorescent nanodiamond nitrogen-vacancy centres inside living human HeLa cells, and measure their location, orientation, spin levels and spin coherence times with nanoscale precision. Quantum coherence was measured through Rabi and spin-echo sequences over long (>10 h) periods, and orientation was tracked with effective 1° angular precision over acquisition times of 89 ms. The quantum spin levels served as fingerprints, allowing individual centres with identical fluorescence to be identified and tracked simultaneously. Furthermore, monitoring decoherence rates in response to changes in the local environment may provide new information about intracellular processes. The experiments reported here demonstrate the viability of controlled single spin probes for nanomagnetometry in biological systems, opening up a host of new possibilities for quantum-based imaging in the life sciences. The orientation, spin coherence times and spin energy levels of individual nanodiamond nitrogen-vacancy centres have been measured inside living human cells with nanoscale precision.
594 citations
TL;DR: Recent developments in hydrogen-bonded LbL-assembled materials will be discussed, focusing on the design of materials with enhanced stimuli-responsive characteristics, specifically films/capsules that afford controlled loading and release of therapeutic cargo for application in vitro and in vivo.
Abstract: Over the last two decades the layer-by-layer (LbL) assembly technique has become a highly versatile platform for the synthesis of nanoengineered thin films and particles The widespread need for highly functional and responsive materials for applications in biomedicine—such as drug and gene delivery—has recently led to considerable efforts in the assembly of LbL materials, particularly films that can be subsequently stabilised and functionalised through a range of chemistries In this tutorial review, recent developments in hydrogen-bonded LbL-assembled materials will be discussed, focusing on the design of materials with enhanced stimuli-responsive characteristics Emphasis will be given to materials engineered for biomedical applications, specifically films/capsules that afford controlled loading and release of therapeutic cargo for application in vitro and in vivo
320 citations
TL;DR: PGA-dopamine conjugates were synthesized and assembled onto silica particles to yield biodegradable capsules with tunable degradation properties that are expected to find application in diverse areas, including drug and gene delivery.
Abstract: PGA-dopamine conjugates (PGAPDA) were synthesized and assembled onto silica particles to yield biodegradable capsules with tunable degradation properties. Increasing the dopamine content results in thicker films with a concomitant reduction in the degradation kinetics. These tailored capsules are expected to find application in diverse areas, including drug and gene delivery.
117 citations
TL;DR: This Perspective highlights an important development by Poon et al. on tumor targeting in vivo using LbL-engineered nanoparticles containing a pH-responsive poly(ethylene glycol) (PEG) surface layer and explores future directions in this field.
Abstract: Layer-by-layer (LbL)-engineered particles have recently emerged as a promising class of materials for applications in biomedicine, with studies progressing from in vitro to in vivo. The versatility of LbL assembly coupled with particle templating has led to engineered particles with specific properties (e.g., stimuli-responsive, high cargo encapsulation efficiency, targeting), thus offering new opportunities in targeted and triggered therapeutic release. This Perspective highlights an important development by Poon et al. on tumor targeting in vivo using LbL-engineered nanoparticles containing a pH-responsive poly(ethylene glycol) (PEG) surface layer. Further, we summarize recent progress in the application of LbL particles in the fields of drug, gene, and vaccine delivery and cancer imaging. Finally, we explore future directions in this field, focusing on the biological processing of LbL-assembled particles.
111 citations
TL;DR: The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported.
Abstract: The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.
101 citations
TL;DR: The development of responsive polymeric carriers for intracellular drug/gene delivery is a burgeoning research area, due to the enhanced therapeutic benefits offered by these systems over traditional administration methods and the need to design carriers that have engineered sensitivity to such environments to maximize cargo release behavior and ultimately therapeutic outcomes.
Abstract: The assembly of responsive layer-by-layer-assembled click polymer capsules that exhibit dual-responsive cargo release mechanisms for the controlled release of cargo is reported. The capsules show reversible size changes between pH 6 and 7.4. The synergistic effects of pH and redox-potential allow for rapid and efficient cargo release at simulated intracellular conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
100 citations
TL;DR: This review focuses on self-assembled carriers such as liposomes, polymer micelles and polymersomes, and carriers prepared through templated-assembly, for example, layer-by-layer assembled capsules and PRINT (particle replication in non-wetting templates) particles.
Abstract: Improving therapeutic delivery to the body will have significant benefits for the treatment of a variety of diseases. Incorporating drugs inside engineered colloidal carriers is a promising approach that can lead to improved drug delivery. Such carriers offer a number of advantages, as they can protect therapeutic cargo from degradation by the body, limit potentially harmful side effects of the drug, and also allow targeted drug delivery to the desired site of action. Colloidal carriers have the potential to enable clinical use of a number of therapeutics, such as siRNA and peptides, which if administered in their naked form can degrade before demonstrating a viable therapeutic effect. A number of challenges, such as efficient therapeutic loading into the carrier, targeted and specific delivery in the body whilst evading biological defence mechanisms, and controlled release of therapeutically active cargo, must be met for these systems to be clinically relevant. In this review, we focus on recent advances and some of the pertinent challenges faced in developing clinically relevant colloidal drug carriers. We primarily focus on self-assembled carriers such as liposomes, polymer micelles and polymersomes, and carriers prepared through templated-assembly, for example, layer-by-layer assembled capsules and PRINT (particle replication in non-wetting templates) particles.
97 citations
TL;DR: The use of thiolated poly(methacrylic acid) (PMA SH) to prepare single-component polymer capsules stabilized by disulfi de bonds (Pma SH(disulfiDe) ).
Abstract: Redox-responsive polymer capsules stabilized by disulfide bonds and loaded with hydrophobic cargo are prepared by templating mesoporous silica particles via layer-by-layer assembly. The thiols and disulfide bonds in the capsules interact with the exofacial thiols on the cell membrane, which regulate cellular association and cargo release from the capsules. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
96 citations
TL;DR: Evidence suggests that empty micro Capsules can induce a perturbation of the intracellular environment, which causes the activation of a cell safeguard mechanism that may limit the therapeutic effect of the microcapsules in tumor cells.
Abstract: In this report, we describe the delivery of small interfering RNA (siRNA) using LbL-assembled microcapsules. The microcapsules are based on negatively charged poly(methacrylic acid) nanometer thin films containing cross-linking disulfide bonds. One system is polycation-free and another contains polylysine for siRNA complexation in the microcapsule void. When microcapsules containing a siRNA targeting survivin were delivered to PC-3 prostate cancer cells, a significant inhibition of the expression of the antiapoptotic protein was observed. However, down-regulation of survivin was also observed in PC-3 cells exposed to microcapsules embedded with a scrambled siRNA as well as in cells treated with empty microcapsules. These findings indicate a capsule-dependent off-target effect, which is supported by a reduction in the expression of other survivin-unrelated proteins. The microcapsules and their polymeric constituents do not affect cell proliferation, as determined by a metabolic assay, even after 4 days of ...
95 citations
TL;DR: This Perspective describes particle-based multicompartment systems, detailing the building blocks and assembly approaches employed to produce each subcompartmentalized system and the properties that contribute to the performance of multicompartments systems in diverse applications.
Abstract: In recent years, interest in mimicking the complex hierarchical architectures and functionalities of biological systems and associated spatially confined reactions has led to the design and synthesis of a range of multicompartment particles. Multicompartmentalization allows the incorporation of a range of structures in a single particle, thus allowing optimization of physicochemical properties of the assembly (e.g., permeability, stability, stimuli-response) and various multiple, spatially separated reactions. In this Perspective, we describe particle-based multicompartment systems, detailing the building blocks and assembly approaches employed to produce each subcompartmentalized system. The properties that contribute to the performance of multicompartment systems in diverse applications are also discussed, with a focus on coupled enzymatic reactions in confined volumes. The challenges associated with these assemblies for encapsulated reactions are identified and further directions and plausible developm...
93 citations
TL;DR: This perspective begins with a brief introduction of the assembly techniques that are commonly employed for the synthesis of nanostructured polymer materials, followed by discussions on how the interfaces influence the properties and thus the functionalities of the polymer materials prepared.
Abstract: In recent years, interfacial properties have been tailored with nanostructured polymer assemblies to generate materials with specific properties and functions for application in diverse fields, including biomaterials, drug delivery, catalysis, sensing, optics and corrosion. This perspective begins with a brief introduction of the assembly techniques that are commonly employed for the synthesis of nanostructured polymer materials, followed by discussions on how the interfaces influence the properties and thus the functionalities of the polymer materials prepared. Applications of the interfacial polymer nanostructures, particularly for the immobilization and encapsulation of cargo, are then reviewed, focusing on stimuli-responsive cargo release from the polymer nanostructured assemblies for controlled delivery applications. Finally, future research directions in these areas are briefly discussed.
TL;DR: The coencapsulation of glutathione reductase and disulfide-linked polymer-oligopeptide conjugates into capsosomes, polymer carrier capsules containing liposomal subcompartments is reported.
Abstract: We report the coencapsulation of glutathione reductase and disulfide-linked polymer-oligopeptide conjugates into capsosomes, polymer carrier capsules containing liposomal subcompartments. The architecture of the capsosomes enables a temperature-triggered conversion of oxidized glutathione to its reduced sulfhydryl form by the encapsulated glutathione reductase. The reduced glutathione subsequently induces the release of the encapsulated oligopeptides from the capsosomes by reducing the disulfide linkages of the conjugates. This study highlights the potential of capsosomes to continuously generate a potent antioxidant while simultaneously releasing small molecule therapeutics.
TL;DR: Artifi cial cells, although far less complex than their biological counterparts, can exhibit a hierarchical structure with a large number of subcompartments confi ned within a structurally stable scaffold that is engineered for therapeutic cell mimicry via the encapsulation and/or conversion of biologically active materials.
Abstract: Biological cells are able to perform multiple complex reactions within confi ned environments, owing to their structures comprising internal subcompartments (e.g., cell organelles). [ 1 ] Artifi cial cells, [ 2–4 ] although far less complex than their biological counterparts, can exhibit a hierarchical structure with a large number of subcompartments confi ned within a structurally stable scaffold. Such systems are engineered for therapeutic cell mimicry via the encapsulation and/or conversion of biologically active materials. [ 5 ]
TL;DR: These films exhibit specific deconstruction properties under simulated intracellular reducing conditions, but remain stable at physiological pH, suggesting potential applications in controlled drug release, and showed negligible toxicity to human cells.
Abstract: Nano-/micrometer-scaled films and capsules made of low-fouling materials such as poly(ethylene glycol) (PEG) are of interest for drug delivery and tissue engineering applications. Herein, the assembly and degradation of low-fouling, alkyne-functionalized PEG (PEG(Alk) ) multilayer films and capsules, which are prepared by combining layer-by-layer (LbL) assembly and click chemistry, are reported. A nonlinear, temperature-responsive PEG(Alk) is synthesized, and is then used to form hydrogen-bonded multilayers with poly(methacrylic acid) (PMA) at pH 5. The thermoresponsive behavior of PEG(Alk) is exploited to tailor film buildup by adjusting the assembly conditions. Using alkyne-azide click chemistry, PEG(Alk)/PMA multilayers are crosslinked with a bisazide linker that contains a disulfide bond, rendering these films and capsules redox-responsive. At pH 7, by disrupting the hydrogen bonding between the polymers, PEG(Alk) LbL films and PEG(Alk) -based capsules are obtained. These films exhibit specific deconstruction properties under simulated intracellular reducing conditions, but remain stable at physiological pH, suggesting potential applications in controlled drug release. The low-fouling properties of the PEG films are confirmed by incubation with human serum and a blood clot. Additionally, these capsules showed negligible toxicity to human cells.
TL;DR: This work investigates fundamental parameters that govern the structural integrity and the capability of PMA HCs to encapsulate macromolecular cargo and introduces a new strategy to achieve disulfide cross-linking for PMAHCs via a thiol-disulfide exchange in order to obtain capsules with superior cargo retention characteristics.
Abstract: Nanoengineered poly(methacrylic acid) hydrogel capsules (PMA HCs) are promising candidate carriers for biomedical applications, especially in the areas of drug delivery, encapsulated catalysis, and cell mimicry. The assembly, stability, and degradation of these carriers, as well as their use for the encapsulation of therapeutics, have received considerable attention. However, tailoring the permeability properties of PMA HCs to various types of cargo remains largely unexplored. Herein, we investigate fundamental parameters that govern the structural integrity and the capability of PMA HCs to encapsulate macromolecular cargo. The thiol content of the constituent polymers and the number of deposited polymer layers are shown to be key factors in controlling cargo retention within the PMA HCs. We further introduce a new strategy to achieve disulfide cross-linking for PMA HCs via a thiol−disulfide exchange in order to obtain capsules with superior cargo retention characteristics. Finally, we provide evidence fo...
TL;DR: In this paper, cubosomes were embedded within a multilayer assembly of oppositely charged polyelectrolytes [poly(allylamine hydrochloride) and poly(styrene sulfonate)] on planar silica substrates.
Abstract: Microcapsules created by the layer-by-layer (LbL) polyelectrolyte adsorption technique have been sub-compartmentalised by embedding cubic mesophase lipid nanoparticles (cubosomes™) into the capsule shell wall. Monoolein and phytantriol cubosomes™ containing fluorescent lipid and/or positively charged surfactant were first analysed for stability viadynamic light scattering, microelectrophoresis, and small angle X-ray scattering techniques. Once nanoparticle stability was confirmed, cubosomes™ were embedded within a multilayer assembly of oppositely charged polyelectrolytes [poly(allylamine hydrochloride) and poly(styrene sulfonate)] on planar silica substrates. Deposition of each layer was monitored using a quartz crystal microbalance with dissipation monitoring. These findings were then correlated to the growth of polyelectrolyte films incorporating cubosomes™ onto silica microparticles, where ζ-potential measurements were used to monitor the deposition of each subsequent layer. Small angle X-ray scattering experiments provided verification that cubosomes™ remained structurally intact when embedded within the polyelectrolyte matrix. Upon removal of the silica core, stable microcapsules containing one layer of embedded cubic nanoparticles were obtained. A diversity of molecular encapsulation matrices is offered through the capsule core, polyelectrolyte layers, and the embedded cubosomes™ of these sub-compartmentalised, nanostructured microcapsules.
TL;DR: Low-fouling poly(N-vinyl pyrrolidone) (PVPON) capsules assembled via hydrogen bonding and stabilized using covalent cross-linking are reported, suggesting that PEG₈-stabilized capsules were more efficiently cross-linked, and hence displayed higher plasmid encapsulation.
TL;DR: The continuous assembly of polymers (CAP) via atom transfer radical polymerisation (ATRP) is reported as an efficient approach for the preparation of dense, cross-linked, nanoscale engineered films as surface coatings, hollow capsules and replica particles.
TL;DR: Four Polyrotaxanes (PRXs) consisting of linear poly(ethylene glycol) (PEG) and multiple threaded α -cyclodextrins ( α CD) exhibit a number of intriguing and tunable properties, including the improved multivalent binding of threaded α CDs to ligands.
Abstract: 4 Polyrotaxanes (PRXs) [ 1 ] consisting of linear poly(ethylene glycol) (PEG) and multiple threaded α -cyclodextrins ( α CD) [ 2 ] exhibit a number of intriguing and tunable properties. [ 3 , 4 ] An illustrative example is the improved multivalent binding of threaded α CDs to ligands, which is a direct result of the rotational freedom and sliding mobility experienced by the α CDs in these PRXs. [ 5 ]
TL;DR: In this paper, a highly generalizable, surface-confined, continuous polymer assembly process, amenable to various substrates, reaction conditions and macromolecules, enables the synthesis of a range of nanoscale supported and freestanding cross-linked polymer films.
Abstract: A highly generalizable, surface-confined, continuous polymer assembly process, amenable to various substrates, reaction conditions and macromolecules, enables the synthesis of a range of nanoscale supported and freestanding cross-linked polymer films. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
TL;DR: Bromoisobutyramide-modified silica templates facilitate the formation of bio-functional thin films made of a range of biopolymers without the need for covalent cross-linking.
Abstract: Bromoisobutyramide (BrIBAM)-modified silica templates facilitate the formation of bio-functional thin films made of a range of biopolymers (e.g., polypeptides, nucleic acids or polysaccharides). Upon template removal, non-covalent free-standing biopolymeric assemblies (e.g., hollow capsules or replicated spheres and fibers) are formed without the need for covalent cross-linking.
TL;DR: The preparation of layer-by-layer (LbL) assembled, biodegradable, covalently stabilized capsules with tunable degradation properties with facile tailoring of the degradation kinetics is promising for the design of tailored drug-delivery vehicles.
Abstract: Herein we report the preparation of layer-by-layer (LbL) assembled, biodegradable, covalently stabilized capsules with tunable degradation properties. Poly(l-glutamic acid) modified with alkyne moieties (PGAAlk) was alternately assembled with poly(N-vinyl pyrrolidone) (PVPON) on silica particles via hydrogen-bonding. The films were cross-linked with a bis-azide linker, followed by removal of the sacrificial template and PVPON at physiological pH through hydrogen bond disruption, yielding one-component PGAAlk capsules. To control the kinetics and location of capsule degradation, a number of approaches were investigated. First, a degradable bis-azide cross-linker was incorporated into the inherently enzymatically degradable capsules. Second, we assembled low-fouling capsules composed of nondegradable poly(N-vinyl pyrrolidone-ran-propargyl acrylate) (PVPONAlk) via hydrogen bonding with poly(methacrylic acid) (PMA) and combined this with the aforementioned system (PGAAlk/PVPON) to produce stratified hybrid ca...
TL;DR: A one-pot ultrasonic procedure has been developed as a versatile route for synthesizing polymer-coated microspheres that have potential application as drug delivery vehicles.
TL;DR: In this article, the combination of click chemistry and layer-by-layer assembly provides a useful and convenient means of preparing functional, covalently stabilized films and capsules, and they examine var...
Abstract: The combination of click chemistry and layer-by-layer (LbL) assembly provides a useful and convenient means of preparing functional, covalently stabilized films and capsules. Herein, we examine var...
TL;DR: The outlined surface modification of capsosomes contributes to the development of these systems toward functional therapeutic artificial cells as well as investigating the fouling characteristics of this carrier system.
Abstract: Capsosomes, polymer hydrogel capsules containing intact liposomal subcompartments, represent a promising platform toward the assembly of cell-like systems. Compartmentalized assembly plays a key role in the creation of therapeutic artificial cells, which focuses on enzymatic activities to degrade waste products or to support the synthesis of biomolecules. A fundamental aspect that governs the success of continuous enzymatic reactions in capsosomes is the long-term stability of the liposomal subunits within the polymer hydrogel capsules at physiological conditions, as they are subject to degradation in the presence of lipases. In this study, the outer membrane of the capsosomes was PEGylated by immobilizing graft copolymers of poly(methacrylic acid) (PMA) and poly(ethylene glycol) (PEG), and the fouling characteristics of this carrier system were investigated by incubation with bovine serum albumin. The influence of PEGylation on the stability of the liposomal subcompartments in the presence of phospholipases in different media was assessed. Diffusion of lipases across the multilayered membrane of the carrier capsules was hindered when the capsules were coated with PEG molecules. Furthermore, the rate of degradation of the liposomal subunits in PEGylated capsosomes was found to be three times higher when the subcompartments were “free-floating” (i.e., not membrane associated) in the capsules. The outlined surface modification of capsosomes contributes to the development of these systems toward functional therapeutic artificial cells.
TL;DR: The delamination technique provides a simple method to analyze the early stages of film chemistry for plasma polymer thin films by depositing the PP film onto an ionic bonded surface such as a sodium chloride crystal.
Abstract: We describe a new method to characterize the underside (substrate interface) of plasma polymer (PP) thin films via their simple delamination from a sodium chloride single crystal substrate. By depositing the PP film onto an ionic bonded surface such as a sodium chloride crystal, the PP films investigated were easily delaminated from the substrate. Two plasma polymer films deposited from 1-bromopropane (BrPP) and allylamine (AAPP) were used to exemplify this new technique. The top- and underside (substrate-plasma polymer interface) of the films were examined by X-ray photoelectron spectroscopy (XPS) and synchrotron-based near edge X-ray adsorption fine structure (NEXAFS) spectroscopy. The results demonstrate that both films exhibit heterogeneous film structures with their chemical composition and levels of unsaturated species. The underside of both the BrPP and the AAPP films exhibited higher concentrations of oxygen, while their topsides contained higher levels of unsaturated species. These results provide useful insights into the BrPP and AAPP film formation and the chemistry. The delamination technique provides a simple method to analyze the early stages of film chemistry for plasma polymer thin films. Furthermore, this approach opens new opportunities for additional studies on the mechanisms and fundamentals of plasma polymer thin film formation with various monomers.
TL;DR: It is demonstrated that G15-mer oligonucleotides grafted to a polymer chain preserve the ability to self-assemble into ordered structures, as well as residual and functional quadruplex moieties that can be used to effectively bind therapeutic agents.
Abstract: The assembly of multifunctional nanostructures bearing G-quadruplex motifs broadens the prospects of using G-quadruplexes as therapeutic carriers. Herein, we report the synthesis and characterization of an oligodeoxyguanosine, G15-mer polymer conjugate. We demonstrate that G15-mer oligonucleotides grafted to a polymer chain preserve the ability to self-assemble into ordered structures. The G-quadruplex-polymer conjugates were assembled onto a surface via hybridization with 30-mer cytosine strands, C30-mer, using a layer-by-layer approach to form microcapsules. A mechanism for the sequential assembly of the multilayer films and microcapsules is presented. We further investigate the photophysical behavior of porphyrin TMPyP4 bound to multilayer-coated particles. This study shows that the multilayer films bear residual and functional quadruplex moieties that can be used to effectively bind therapeutic agents.
28 Aug 2011
TL;DR: In this paper, an optically detected magnetic resonance of individual fluorescent nanodiamond nitrogen-vacancy centres inside living human HeLa cells, and measured their spin levels and spin coherence times while tracking their location and orientation with nanoscale precision.
Abstract: We have demonstrated optically detected magnetic resonance of individual fluorescent nanodiamond nitrogen-vacancy centres inside living human HeLa cells, and measured their spin levels and spin coherence times while tracking their location and orientation with nanoscale precision. Quantum coherence was measured through Rabi and spin-echo sequences over long (>10 h) periods, and orientation was tracked with 1° angular precision in 89 ms acquisition time. Individual centres were identified optically by their electron spin resonance spectrum, allowing simultaneous tracking of many otherwise identical flourescent particles. In addition, variation in the decoherence rates was linked to changes in the local environment inside the cells, representing a new non-destructive imaging modality for intracellular biology.
01 Jan 2011
TL;DR: This chapter presents approaches to engineer stimuli-responsive characteristics into multilayers to facilitate sensing, drug loading, and drug release, and covers functionalization of the surface to impart stealth-like and targeting properties.
Abstract: Techniques to nanoengineer the surface properties of thin films are vital to the development of materials for advanced applications in areas such as energy, biomedicine, and optics. The layer-by-layer (LbL) assembly technique is a premier approach to design thin films as it is simple, versatile, and offers precise control over properties of the films produced. Recently, this technique has been applied to the synthesis of hollow capsules that have application in sensing and drug delivery. Hollow capsules are prepared by the assembly of a nanostructured film on a sacrificial colloidal template, followed by core removal. In this chapter, we highlight three main aspects of research required for the design of nanoengineered LbL capsules. First, we present approaches to engineer stimuli-responsive characteristics into multilayers to facilitate sensing, drug loading, and drug release; second, we cover functionalization of the surface to impart stealth-like and targeting properties; and finally, we discuss approaches for loading different therapeutics into the interior of the capsule. The final section highlights some of the recent applications of LbL capsules in the area of biomedicine.