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The development of nanozymes, artificial enzymes made from inorganic nanoparticles, is widely studied due to their affordability, durability, and strength. Gold nanoparticles (AuNPs) are employed to imitate peroxidase, glucose oxidase, lactate oxidase, superoxide dismutase, and catalase. The last one transforms intracellular hydrogen peroxide into molecular oxygen, whose deficiency is characteristic of the hypoxic tumor microenvironment. Thus, gold nanoparticles are thought to enhance the overall effectiveness of photodynamic therapy. However, the enzyme‐like activity of nanoparticles rapidly decreases in biological media, due to the aggregation and formation of the so‐called "protein corona". In this study, polymeric submicrocapsules loaded with AuNPs and a photodynamic dye are fabricated via Layer‐by‐Layer (LbL) assembly. The enhancement of photodynamic treatment efficacy by in situ production of oxygen by the catalase‐like effect of AuNPs is investigated. Polymeric capsules are thoroughly characterized in terms of physicochemical and catalytic properties, and as a proof of concept, their therapeutic potential is evaluated in vitro. Furthermore, encapsulated AuNPs shows significantly lower aggregation both upon storage and during the reaction course. The results shows that the polymer capsules, containing AuNPs and photodynamic dye, show significantly higher light‐induced cytotoxicity in comparison to the individual photodynamic dye, suggesting a synergistic effect between the formation of molecular oxygen by catalase‐like gold nanozymes and photodynamic action. [ABSTRACT FROM AUTHOR]

Polymer Ca-alginate capsules with rejuvenator bring a high healing level for asphalt concrete under dry healing environments; however, the healing levels of bituminous mixtures containing capsules under water healing conditions are still unknown. In view of this, this study aimed at exploring the healing levels of asphalt concrete containing polymer capsules under various solution healing conditions following cyclic loads. This study involved the preparation of capsules, followed by the evaluation of their morphological characteristics, resilience to compression, thermal endurance, and rejuvenator content. The assessment of the healing properties of asphalt concrete utilizing capsules was conducted through a fracture–heal–refracture examination. This study conducted Fourier transform infrared spectrum experiments to determine the rejuvenator release ratio of capsules under dry conditions and the remaining rejuvenator content in extracted bituminous binder from capsule–asphalt concrete after solution treatment. Meanwhile, a dynamic shear rheometer was utilized to investigate the rheological characteristics of asphalt binder. Results revealed that the healing ratios of capsule–asphalt concrete beams under a dry healing environment were significantly higher than that of beams under various solution healing conditions, and the alkali solution has the worst effect on the improvement in healing ratio. The coupled impact of moisture intrusion and ion erosion resulted in an enhancement of complex modulus of asphalt binder while concurrently reducing its phase angle. Consequently, the restorative capacity of the asphalt binder was weakened. [ABSTRACT FROM AUTHOR]

The generation of multi-functional capsules often requires the sequential deposition of different components on the surface of bubbles or drops. Batch-based methods lack fine control over the capsule sizes, including risk of fusion, and cannot ensure identical environments for each capsule. To overcome these issues, different micro/milli-fluidic methods have been developed in the past. However, a major challenge remains in combining an explicit and flexible control over the capsule generation and their residence time in the different solutions within the same device. Using for the first time the example of bubbles covered by layers of oppositely charged polyelectrolytes (PSS/PAH), we introduce an original millifluidic Lab-on-a-Chip device with two novel functions: (1) Size and separation of the bubbles are tuned at constant flow conditions via gas injection through a movible, circular dispense tip into the cross-flow of a rectangular channel. We provide a detailed exploration of the bubbling parameters together with physical justification of the observations. (2) The device exploits gravity to make the generated bubbles rise between horizontally stacked millifluidic chips containing each the controlled flow of a specific polyelectrolyte solution. In analogy with electric circuits, we show how the flow resistance of each chip can be adapted such that bubbles move smoothly between them while avoiding undesired mixing of the solutions. We show first examples of obtained multilayer capsules and discuss their peculiar features, in particular, their outstanding stability with respect to coalescence and dissolution. While our methods use polyelectrolyte assembly on bubbles, they can be readily transferred to other types of solutions or even to drops and particles. [Display omitted] • New millifluidic method exploits mobile dispensing tip to tune bubbling. • Bubble size and spacing are independently controlled. • Novel method moves bubbles between strata of a millifluidic chip by gravity. • Flow of bubbles through alternating strata creates multilayer PSS/PAH capsules. • Obtained capsules have lifetimes of the order of several months. [ABSTRACT FROM AUTHOR]

The encapsulation of fragile biomacromolecules is crucial in many biotechnological applications but remains challenging. Interfacial complexation (IC) in water‐in‐oil emulsions proves to be an efficient process for the formation of protective polymer layers at the surface of capsule‐precursor water droplets. In this work, the enhancement of conventional IC by introducing thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) strands in the interfacial polymer layer is described. Surfactant‐polymer IC is implemented in water‐in‐fluorocarbon oil emulsions between a water‐soluble poly(L‐lysine)‐g‐poly(N‐isopropylacrylamide) cationic copolymer (PLL‐g‐PNIPAM) and an oil‐soluble anionic surfactant. Fluorescence imaging demonstrates that the thermal collapse transition of PNIPAM strands, triggered by gentle heating, induces an enrichment of the polymer layer initially formed by IC. Spontaneous co‐precipitation of nanoparticles initially dispersed in the aqueous cores—with no specific treatment—is also achieved upon PNIPAM transition. This process is leveraged to irreversibly segregate these nanoparticles in the interfacial polymer layer, resulting in gel‐like mixed shells. Thermo‐enhancement of conventional IC is thus a promising approach for the straightforward formation, strengthening, and functionalization of capsule shells. As implemented in mild conditions, thermo‐enhanced IC is additionally compatible with the encapsulation of proteins, opening new opportunities for delivery systems of biomacromolecules. [ABSTRACT FROM AUTHOR]

Microcapsules of customized shapes offer significant advantages over spherical ones, including enhanced internalization by host cells, improved flow characteristics, and higher packing capacity. In our work, we propose a method for defined-shape polymer capsules fabrication inspired by a traditional “pelmeni” (dumplings) making process. The proposed method is based on soft lithography technique. Two different approaches were demonstrated resulting in polyelectrolyte multilayer and poly(lactic acid) (PLA) capsules both showing monodisperse size and shape distribution with about 7 μm long torpedo-like shape. The PLA capsules are described in terms of their morphology, loading of model cargo molecules, cell cytotoxicity and cell uptake. Carboxyfluorescein, FeCl2 ground crystals and Fe3O4 nanopowder were used as model cargoes for microcapsules. Capsules demonstrate core-shell structure, high loading capacity, hydrophilic molecules retention and internalization by cells without causing toxic effects. The loading efficiency of model cargo in PLA capsules was more than 80 wt%, resulting in about 40 pg of carboxyfluorescein inside each capsule. Proposed method allows unique advantages compared with alternative microencapsulation techniques, such as precise control over capsules' geometry, flexibility for the choice of active cargoes, regardless of their solubility and molecular weight and potential for triggered release mechanism.

Theranostic carriers are widely studied as they can be exploited for both imaging and drug delivery. However, although there are reports suggesting their in vitro level imaging and drug release, there is necessity to display the application (drug delivery/bioimaging/toxicity) at an in vivo level, which is a pre‐requisite for clinical use. Herein, we demonstrate targeted in vivo imaging and biodistribution in Swiss Albino mice solid tumor model using PEGylated polymer capsules encapsulating LaVO4 : Tb3+ nanoparticles (concentration of nanoparticles ∼3.4 μM LaVO4/kg body weight). The capsules were further loaded with doxorubicin for drug delivery which shows tumor regression at different time intervals in tumor mice model. We have further investigated the tumor marker enzymes including β‐glucuronidase, myeloperoxidase, lactate dehydrogenase, and alkaline phosphatase which clearly suggest the reversion to near normal levels after treating with doxorubicin‐loaded polymer capsules for 30 days. comet assay shows DNA damage in tumor cells induced by doxorubicin. Histology studies performed in tumor tissue and liver show obliteration of tumor cells after treating with doxorubicin‐loaded PEGylated polymer capsules encapsulating LaVO4 : Tb3+ nanoparticles. It has also been observed that the weight of the spleen which was enlarged in solid‐tumor‐bearing mice is significantly lower in animals treated with drug‐loaded capsules. [ABSTRACT FROM AUTHOR]

In these years, the encapsulation of proteins for protection and delivery purpose has attracted great interest. In this research, W/O emulsion droplets were used as soft templates and bovine serum albumin (BSA) encapsulated hollow capsules were prepared by liquid-liquid interfacial thiol-disulfide exchange reaction. Block copolymer chains with pendant pyridyl disulfide groups are located at liquid-liquid interface, and upon addition of a macromolecular crosslinking agent with multiple pendant thiol groups into an emulsion, thiol-disulfide interfacial crosslinking reactions lead to the formation of BSA encapsulated hollow capsules. The cleavage of disulfides on the membranes results in the degradation of hollow structures and the release of encapsulated protein molecules. Transmission electron microscopy, scanning electron microscopy, atomic force microscopy, and confocal laser scanning microscopy were employed to characterize the hollow capsules. In comparison with native BSA, BSA molecules encapsulated in the hollow structures show higher catalytic efficiency due to higher local concentration of reactants in the structures. The membranes of the hollow capsules can efficiently protect the encapsulated BSA from hydrolysis by trypsin. [ABSTRACT FROM AUTHOR]

In the past few decades, enormous efforts have been made to synthesize covalent polymer nano/microstructured materials with specific morphologies, due to the relationship between their structures and functions. Up to now, the formation of most of these structures often requires either templates or preorganization in order to construct a specific structure before, and then the subsequent removal of previous templates to form a desired structure, on account of the lack of “self-error-correcting” properties of reversible interactions in polymers. The above processes are time-consuming and tedious. A template-free, self-assembled strategy as a “bottom-up” route to fabricate well-defined nano/microstructures remains a challenge. Herein, we introduce the recent progress in template-free, self-assembled nano/microstructures formed by covalent two-dimensional (2D) polymers, such as polymer capsules, polymer films, polymer tubes and polymer rings.

Polymeric capsules exhibit significant potential for therapeutic applications as microreactors, where the bio-chemical reactions of interest are efficiently performed in a spatial and time defined manner due to the encapsulation of an active biomolecule (e.g., enzyme) and control over the transfer of reagents and products through the capsular membrane. In this work, catalase loaded polymer capsules functionalized with an external layer of tannic acid (TA) are fabricated via a layer-by-layer approach using calcium carbonate as a sacrificial template. The capsules functionalised with TA exhibit a higher scavenging capacity for hydrogen peroxide and hydroxyl radicals, suggesting that the external layer of TA shows intrinsic antioxidant properties, and represents a valid strategy to increase the overall antioxidant potential of the developed capsules. Additionally, the hydrogen peroxide scavenging capacity of the capsules is enhanced in the presence of the encapsulated catalase. The capsules prevent oxidative stress in an in vitro inflammation model of degenerative disc disease. Moreover, the expression of matrix metalloproteinase-3 (MMP-3), and disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), which represents the major proteolytic enzymes in intervertebral disc, are attenuated in the presence of the polymer capsules. This platform technology exhibits potential to reduce oxidative stress, a key modulator in the pathology of a broad range of inflammatory diseases. Statement of Significance Oxidative stress damages important cell structures leading to cellular apoptosis and senescence, for numerous disease pathologies including cancer, neurodegeneration or osteoarthritis. Thus, the development of biomaterials-based systems to control oxidative stress has gained an increasing interest. Herein, polymer capsules loaded with catalase and functionalized with an external layer of tannic acid are fabricated, which can efficiently scavenge important reactive oxygen species (i.e., hydroxyl radicals and hydrogen peroxide) and modulate extracellular matrix activity in an in vitro inflammation model of nucleus pulposus. The present work represents accordingly, an important advance in the development and application of polymer capsules with antioxidant properties for the treatment of oxidative stress, which is applicable for multiple inflammatory disease targets. [ABSTRACT FROM AUTHOR]

Polymer capsules, fabricated either with the aid of a sacrificial template or via the self-assembly of block copolymers into polymer vesicles (polymersomes), have attracted a great deal of attention for their potential use as micro-/nanoreactors and artificial organelles for therapeutic applications. Compared to other biomedical applications of polymer capsules, such as drug delivery vehicles, where the polymer shell undergoes irreversible disruption/rupture that allows the release of the payload, the polymer shell in polymer micro-/nanoreactors has to maintain mechanical integrity while allowing the selective diffusion of reagents/reaction products. In the present review, strategies that permit precise control of the permeability of the polymer shell while preserving its architecture are documented and critiqued. Together with these strategies, specific examples where these polymer capsules have been employed as micro-/nanoreactors as well as approaches to scale-up and optimize these systems along with future perspectives for therapeutic applications in several degenerative diseases are elucidated. [ABSTRACT FROM AUTHOR]

Polymer microcapsules are of particular interest for applications including self‐healing coatings, catalysis, bioreactions, sensing, and drug delivery. The primary way that polymer capsules can exhibit functionality relevant to these diverse fields is through the incorporation of functional cargo in the capsule cavity or wall. Diverse functional and therapeutic cargo can be loaded into polymer capsules with ease using polymer‐stabilized calcium carbonate (CaCO3) particles. A variety of examples are demonstrated, including 15 types of cargo, yielding a toolbox with effectively 500+ variations. This process uses no harsh reagents and can take less than 30 min to prepare, load, coat, and form the hollow capsules. For these reasons, it is expected that the technique will play a crucial role across scientific studies in numerous fields. [ABSTRACT FROM AUTHOR]

We report on a facile and reliable preparation of polypyrrole vessel structures modified with gold nanoparticles that are able to encapsulate organic molecules of biological importance. The polymer is coated onto the surface of aqueous droplets through photopolymerization of the monomer. When gold nanoparticles and/or biomolecules are contained in the droplets, these species become incorporated within the formed polymer microvessels. Herein, we provide thorough physicochemical characterization of the polymer structures including electron and optical microscopy, spectroscopy (steady state and time-resolved fluorescence, XPS, XRF) and other experimental techniques. Polymer microvessels are promising as smart drug carriers for new experimental therapies. As model drugs we use mRNA cap analogs which are nucleotide-derived compounds that have been shown to be potential anti-cancer agents. We demonstrate that embedding the metallic nanoparticles within the microvessels provides usefully high contrast in micro-computed tomography (microCT) which is promising from the standpoint of monitoring the fate of administered drug carriers inside the body. Moreover, our in vivo studies on rats demonstrate that intravenous administration of the microvessels does not evoke acute toxicity or death of the animals. [ABSTRACT FROM AUTHOR]

Abstract: Polyelectrolyte multilayer (PEM) capsules engineered with active elements for targeting, labeling, sensing and delivery hold great promise for the controlled delivery of drugs and the development of new sensing platforms. PEM capsules composed of biodegradable polyelectrolytes are fabricated for intracellular delivery of encapsulated cargo (for example peptides, enzymes, DNA, and drugs) through gradual biodegradation of the shell components. PEM capsules with shells responsive to environmental or physical stimuli are exploited to control drug release. In the presence of appropriate triggers (e.g., pH variation or light irradiation) the pores of the multilayer shell are unlocked, leading to the controlled release of encapsulated cargos. By loading sensing elements in the capsules interior, PEM capsules sensitive to biological analytes, such as ions and metabolites, are assembled and used to detect analyte concentration changes in the surrounding environment. This Review aims to evaluate the current state of PEM capsules for drug delivery and sensing applications. [Copyright &y& Elsevier]

Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive techniques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thoroughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multifunctional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized. [Display omitted] • Strategies to impart multifunctional properties to LbL capsules are reviewed. • The core, the multilayer membrane and the outer layer are individually considered. • Biomedical applications are summarized in three comprehensive tables. • Current challenges of LbL capsules to reach the clinical practice are discussed. [ABSTRACT FROM AUTHOR]

Highlights: [•] Six types of amine corrosion inhibitor were loaded into nanocapsules. [•] Encapsulation and release of amines were affected by their intrinsic properties. [•] Amines with OH groups showed better corrosion resistance than those without OH. [•] Better corrosion performances were due to repassivation with self-healing protection. [Copyright &y& Elsevier]

The article discusses a study on an electrophoretic polymer assembly (EPA) technique for preparing nanocapsules and microcapsules. The EPA technique involves using electrophoresis to produce particles coated with multiple polymer layers and polymer multilayer capsules. The technique also uses agarose as a natural microfluidic hydrogel to immobilize the particles. The implication of the technique for layer-by-layer assembly of polymers is explained.

Abstract: Polymer capsules containing multiple liposomes, termed capsosomes, are a promising new concept toward the design of artificial cells. Herein, we report on the fundamental aspects underpinning the assembly of capsosomes. A stable and high loading of intact liposomal cargo into a polymer film was achieved by non-covalently sandwiching the liposomes between a tailor-made cholesterol-modified poly(l-lysine) (PLLc) precursor layer and a poly(methacrylic acid)-co-(cholesteryl methacrylate) (PMAc) capping layer. The film assembly, optimized on planar surfaces, was successfully transferred onto colloidal substrates, and a polymer membrane was subsequently assembled by the alternating adsorption of poly(N-vinyl pyrrolidone) (PVP) and thiol-modified poly(methacrylic acid) (PMASH) onto the pre-adsorbed layer of liposomes. Upon removal of the silica template, stable capsosomes encapsulating the enzyme luciferase or β-lactamase within their liposomal sub-compartments were obtained at both assembly (pH 4) and physiological conditions (pH 7.4). Excellent retention of the liposomes and the enzymatic cargo within the polymer carrier capsules was observed for up to 14 days. These engineered capsosomes are particularly attractive as autonomous microreactors, which can be utilized to repetitively add smaller reactants to cause successive distinct reactions within the capsosomes and simultaneously release the products to the surrounding environment, bringing these systems one step closer toward constructing artificial cells. [Copyright &y& Elsevier]

Abstract: Over the last 15 years, development of the layer-by-layer (LbL) technique for preparing thin films has greatly improved control over the physical and chemical properties of thin films. When applied to colloidal particles, the LbL technology permits the formation of hollow capsules with engineered features, including size, shape, composition and function. In this review, we outline the potential applications of LbL assembled micro- and nanometer-sized capsules. These lie principally in the areas of drug delivery, sensing, catalysis and microreactors. We focus on the potential use of LbL capsules as drug delivery vehicles and, specifically, on methods for encapsulating and releasing molecules from capsules as well as on targeting capsules to cells. [Copyright &y& Elsevier]

Abstract: In recent years, the layer-by-layer (LbL) self-assembly technique has grown strong in its influence on chemistry, physics, materials science, and biology. One of the emerging trends in the area is the growing interest in design of polyelectrolyte multilayer films (PEMs) with specific response characteristics. This approach is significantly facilitated by the versatility and flexibility of the LbL technique. In this review, fundamental aspects of construction of PEMs responsive to a variety of external stimuli such as pH, ionic strength, temperature, light, magnetic field or specific biological moieties, and their possible applications are discussed. [Copyright &y& Elsevier]

Engineering of colloidal particles and capsules despite substantial progress is still facing a number of unsolved issues including low loading capacity, non-uniform size and shape of carriers, tailoring different functionalities and versatility to encapsulated cargo. In this work, we propose a method for defined-shaped functionally asymmetric polymer capsule fabrication based on a soft lithography approach. The developed capsules consist of two classes of polymers - the main part "cup" is made out of polyelectrolyte multilayers (PAH-PSS) and "lid" is made of biodegradable polyether (PLGA). Asymmetric capsules combine advantages from both traditional layer-by-layer capsules and recently developed printed "pelmeni" capsules. This combination provides stimuli-responsiveness due to polyelectrolyte multilayer properties differing from PLGA. The inner volume of capsules can be loaded with a variety of active compounds and the capsule's geometry is defined due to the soft-lithography method. Capsules have a core-shell structure and monodisperse size distribution. Three methods to trigger cargo release have been demonstrated, namely temperature treatment, ultrasonication and pH shift. Steroidal drug dexamethasone was used to illustrate the applicability of the systems for triggered drug release. The application of proposed asymmetric capsules includes but is not limited to pharmacology, diagnostics, sensors, micro- and nanoreactors and chemical actuators., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chitosan belongs to the group of biopolymers with increasing range of potential applications therefore searching for new raw materials as well as new techniques of obtaining of this polysaccharide are currently a subject of interest of many scientists. Presented manuscript describes preparation of chitosan from crickets. Obtainment of final product required a number of processes aimed at removal of undesirable substances such as waxes, mineral salts, proteins or pigments from above-mentioned insects. Chemical structure of fractions obtained after each step was compared with the structure of commercial chitosan by means of techniques such as X-ray diffraction and FT-IR spectroscopy. Final product was subsequently used for preparation of polymer capsules that were modified with active substance characterized by antibacterial and anticancer activity—nisin. Next, sorption capacity of obtained materials was evaluated as well as a release profile of active substance in different environments. Based on the conducted research it can be concluded that crickets constitute an alternative for shellfish and other conventional sources of chitosan. Furthermore, obtained capsules on the basis of such prepared chitosan can be considered as drug delivery systems which efficiency of release of active substance is bigger in alkaline environments. [ABSTRACT FROM AUTHOR]

The anisotropy in the shape of polymeric particles has been demonstrated to have many advantages over spherical particulates, including bio-mimetic behavior, shaped-directed flow, deformation, surface adhesion, targeting, motion, and permeability. The layer-by-layer (LbL) assembly is uniquely suited for synthesizing anisotropic particles as this method allows for simple and versatile replication of diverse colloid geometries with precise control over their chemical and physical properties. This review highlights recent progress in anisotropic particles of micrometer and nanometer sizes produced by a templated multilayer assembly of synthetic and biological macromolecules. Synthetic approaches to produce capsules and hydrogels utilizing anisotropic templates such as biological, polymeric, bulk hydrogel, inorganic colloids, and metal-organic framework crystals as sacrificial templates are overviewed. Structure-property relationships controlled by the anisotropy in particle shape and surface are discussed and compared with their spherical counterparts. Advances and challenges in controlling particle properties through varying shape anisotropy and surface asymmetry are outlined. The perspective applications of anisotropic colloids in biomedicine, including programmed behavior in the blood and tissues as artificial cells, nano-motors/sensors, and intelligent drug carriers are also discussed., (© 2021 Wiley-VCH GmbH.)

In the past few decades, enormous efforts have been made to synthesize covalent polymer nano/microstructured materials with specific morphologies, due to the relationship between their structures and functions. Up to now, the formation of most of these structures often requires either templates or preorganization in order to construct a specific structure before, and then the subsequent removal of previous templates to form a desired structure, on account of the lack of "self-error-correcting" properties of reversible interactions in polymers. The above processes are time-consuming and tedious. A template-free, self-assembled strategy as a "bottom-up" route to fabricate well-defined nano/microstructures remains a challenge. Herein, we introduce the recent progress in template-free, self-assembled nano/microstructures formed by covalent two-dimensional (2D) polymers, such as polymer capsules, polymer films, polymer tubes and polymer rings. [ABSTRACT FROM AUTHOR]

To reduce nonspecific interactions and circumvent biological barriers, low-fouling material of poly(ethylene glycol) (PEG) is most used for the modification of drug nanocarriers. Herein, we report the fabrication of PEG capsules via the free-radical polymerization of linear PEG or 8-arm-PEG using an emulsion templating method for targeted drug delivery. Doxorubicin (DOX) could be loaded in capsules via electrostatic interactions. The obtained capsules composed of 8-arm-PEG result in a lower cell association (2.2%) compared to those composed of linear PEG (7.3%) and, therefore, demonstrate the stealth property. The functionalization of cyclic peptides containing Arg-Gly-Asp (cRGD) on PEG capsules induce high cell targeting to U87 MG cells. A cell cytotoxicity assay demonstrates the biocompatibility of PEG capsules and high drug delivery efficacy of the targeted capsules. The reported capsules with the stealth and targeting property provide a potential platform for improved drug delivery. [ABSTRACT FROM AUTHOR]

Polymer capsules fabricated via the layer-by-layer (LbL) approach have emerged as promising biomedical systems for the release of a wide variety of therapeutic agents, owing to their tunable and controllable structure and the possibility to include several functionalities in the polymeric membrane during the fabrication process. However, the limitation of the capsules with a single functionality to overcome the challenges involved in the treatment of complex pathologies denotes the need to develop multifunctional capsules capable of targeting several mediators and/or mechanisms. Oxidative stress is caused by the accumulation of reactive oxygen species [ e.g. , hydrogen peroxide (H 2 O 2 ), hydroxyl radicals ( • OH), and superoxide anion radicals ( • O 2 - )] in the cellular microenvironment and is a key modulator in the pathology of a broad range of inflammatory diseases. The disease microenvironment is also characterized by the presence of proinflammatory cytokines, increased levels of matrix metalloproteinases, and acidic pH, all of which could be exploited to trigger the release of therapeutic agents. In the present work, multifunctional capsules were fabricated via the LbL approach. Capsules were loaded with an antioxidant enzyme (catalase) and functionalized with a model drug (doxorubicin), which was conjugated to an amine-containing dendritic polyglycerol through a pH-responsive linker. These capsules efficiently scavenge H 2 O 2 from solution, protecting cells from oxidative stress, and release the model drug in acidic microenvironments. Accordingly, in this work, a polymeric microplatform is presented as an unexplored combinatorial approach applicable for multiple targets of inflammatory diseases, in order to perform controlled spatiotemporal enzymatic reactions and drug release in response to biologically relevant stimuli.

Microcapsules formed using a "layer-by-layer" alternating deposition of oppositely charged polyelectrolytes on sacrificial templates have reached high interest because of their facile fabrication procedure using a broad range of materials and tailored properties. However, their practical applications as microcarriers are limited as the capsules commonly suffer from low mechanical stability that can be enhanced by chemical or physical crosslinking but at the expense of decreasing permeability of the capsules' walls. It is demonstrated here that the incorporation of multiwalled carbon nanotubes in a relatively small amount (3.5%) arranged in the direction perpendicular to the capsules' walls led to an almost 20-fold increase of the apparent elastic modulus of the microcapsules as shown using the osmotic pressure method. Importantly, the introduced carbon nanotubes due to their absorption in the near-infrared region and specific arrangement enabled also a light-triggered increase of permeability of the capsules in a reversible, nondestructive manner as shown using fluorescently labeled dextrans of various molar masses. Such results imply durability and facile loading/unloading of the microcapsules that are both crucial for their practical applications as microcontainers and microreactors.

Poly(ethylenimine) (PEI) is frequently used as transfection agent for delivery of nucleic acids to the cytosol. After endocytosis of complexes of PEI and nucleic acids, a fraction of them can escape endosomes/lysosomes and reach the cytosol. One proposed mechanism is the so-called proton sponge effect, which involves buffering of the lysosomal pH by PEI. There are however also reports that report the absence of such buffering. In this work, the buffering capacity of PEI of the lysosomal pH was investigated in situ by combining PEI and pH-sensing ratiometric fluorophores in a single carrier particle. As carrier particles, hereby capsules were used, which were composed of polyelectrolyte walls based on layer-by-layer assembly, with the pH sensors located inside the capsule cavities. In this way, the local pH around individual particles could be monitored during the whole process of endocytosis. Results demonstrate the pH-buffering capability of PEI, which prevents the strong acidification of lysosomes containing PEI. This effect was related to the presence of PEI and was not related to the overall charge of the carrier particles. In case PEI was added in molecular form, no buffering of pH could be observed by endocytosed encapsulated pH-sensing ratiometric fluorophores. Co-localization experiments demonstrated that this was due to the fact that internalized free PEI and the encapsulated pH-sensing ratiometric fluorophores were not located in the same lysosomes. Missing co-localization might explain why also in other studies no pH buffering was found; in the case of co-delivery of PEI, the pH sensors could be clearly observed.

• Langmuir monolayer as a model to study the cellular membrane–capsules interaction. • Membrane–capsule interaction is regulated by varying capsule shell composition. • Investigation of triggered drug release using the model cellular membrane. Submicrocapsules were prepared from diethylaminoethyl dextran (DEAE-D), xanthan gum (XG) and bovine serum albumin (BSA) on oil cores by ultrasonic treatment. These capsules were modified with poly-L-lysine (PLL) via electrostatic adsorption. The behavior of the capsules was investigated at an air–water interface after their introduction into an aqueous subphase. The interaction of the capsules with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer formed on the water surface (model cellular membrane) was studied both upon their introduction under the condensed monolayer and with the use of a dilute colloidal solution of the capsules as a subphase. Biodegradation of the proteinaceous capsules with subsequent oil-core release was demonstrated by influence of pronase. The Langmuir lipid monolayer was found to be a good model for investigation of drug release from the capsules in the presence of the cellular membrane. [ABSTRACT FROM AUTHOR]

The design of magnetic nanostructures whose magnetic heating efficiency remains unaffected at the tumor site is a fundamental requirement to further advance magnetic hyperthermia in the clinic. This work demonstrates that the confinement of magnetic nanoparticles (NPs) into a sub-micrometer cavity is a key strategy to enable a certain degree of nanoparticle motion and minimize aggregation effects, consequently preserving the magnetic heat loss of iron oxide nanocubes (IONCs) under different conditions, including intracellular environments. We fabricated magnetic layer-by-layer (LbL) self-assembled polyelectrolyte sub-micrometer capsules using three different approaches, and we studied their heating efficiency as obtained in aqueous dispersions and after internalization by tumor cells. First, IONCs were added to the hollow cavities of LbL submicrocapsules, allowing the IONCs to move to a certain extent in the capsule cavities. Second, IONCs were coencapsulated into solid calcium carbonate cores coated with LbL polymer shells. Third, IONCs were incorporated within the polymer layers of the LbL capsule walls. In aqueous solution, higher specific absorption rate (SAR) values were related to those of free IONCs, while lower SAR values were recorded for capsule/core assemblies. However, after uptake by cancer cell lines (SKOV-3 cells), the SAR values of the free IONCs were significantly lower than those observed for capsule/core assemblies, especially after prolonged incubation periods (24 and 48 h). These results show that IONCs packed into submicrocavities preserve the magnetic losses, as the SAR values remained almost invariable. Conversely, free IONCs without the protective capsule shell agglomerated and their magnetic losses were strongly reduced. Indeed, IONC-loaded capsules and free IONCs reside inside endosomal and lysosomal compartments after cellular uptake and show strongly reduced magnetic losses due to the immobilization and aggregation in centrosymmetrical structures in the intracellular vesicles. The confinement of IONCs into sub-micrometer cavities is a key strategy to provide a sustained and predictable heating dose inside biological matrices.

In the present study, a capsule system that consists of a stealth carrier based on poly(ethylene glycol) (PEG) and functionalized with bispecific antibodies (BsAbs) is introduced to examine the influence of the capsule shape and size on cellular targeting. Hollow spherical and rod-shaped PEG capsules with tunable aspect ratios (ARs) of 1, 7, and 18 were synthesized and subsequently functionalized with BsAbs that exhibit dual specificities to PEG and epidermal growth factor receptor (EGFR). Dosimetry (variation between the concentrations of capsules present and capsules that reach the cell surface) was controlled through "dynamic" incubation (i.e., continuously mixing the incubation medium). The results obtained were compared with those obtained from the "static" incubation experiments. Regardless of the incubation method and the capsule shape and size studied, BsAb-functionalized PEG capsules showed >90% specific cellular association to EGFR-positive human breast cancer cells MDA-MB-468 and negligible association with both control cell lines (EGFR negative Chinese hamster ovary cells CHO-K1 and murine macrophages RAW 264.7) after incubation for 5 h. When dosimetry was controlled and the dose concentration was normalized to the capsule surface area, the size or shape had a minimal influence on the cell association behavior of the capsules. However, different cellular internalization behaviors were observed, and the capsules with ARs 7 and 18 were, respectively, the least and most optimal shape for achieving high cell internalization under both dynamic and static conditions. Dynamic incubation showed a greater impact on the internalization of rod-shaped capsules (∼58-67% change) than on the spherical capsules (∼24-29% change). The BsAb-functionalized PEG capsules reported provide a versatile particle platform for the evaluation and comparison of cellular targeting performance of capsules with different sizes and shapes in vitro.