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Co-localization of monomers, crosslinkers, and chain-transfer agents (CTA) within self-assembled bilayers in an aqueous suspension enabled the successful directed assembly of nanocapsules using a reversible addition-fragmentation chain transfer (RAFT) process without compromising the polymerization kinetics. This study uncovered substantial influence of the organized medium on the course of the reaction, including differential reactivity based on placement and mobility of monomers, crosslinkers, and CTAs within the bilayer.

The laboratory safety team (LST) movement was triggered in 2012 by Dow Chemical’s exploration of ways to strengthen academic research safety culture from the bottom up. This necessitated a new form...

Vesicle-templated nanocapsules offer a unique combination of properties enabled by robust shells with single-nanometer thickness containing programmed uniform pores capable of fast and selective mass transfer. These capsules emerged as a versatile platform for creating functional devices, such as nanoreactors, nanosensors, and containers for the delivery of drugs and imaging agents. Nanocapsules are synthesized by a directed assembly method using self-assembled bilayers of vesicles as temporary scaffolds. In this approach, hydrophobic building blocks are loaded into the hydrophobic interior of vesicles formed from lipids or surfactants. Pore-forming templates are codissolved with the monomers and cross-linkers in the interior of the bilayer. The polymerization forms a cross-linked shell with embedded pore-forming templates. Removal of the surfactant scaffold and pore-forming templates leads to free-standing nanocapsules with shells containing uniform imprinted nanopores. Development of reliable and scalable synthetic methods for the modular construction of capsules with tunable properties has opened the opportunity to pursue practical applications of nanocapsules. In this Account, we discuss how unique properties of vesicle-templated nanocapsules translate into the creation of functional nanodevices. Specifically, we focus the conversation on applications aiming at the delivery of drugs and imaging agents, creation of fast-acting and selective nanoreactors, and fabrication of nanoprobes for sensing and imaging. We present a brief overview of the synthesis of nanocapsules with an emphasis on recent developments leading to robust synthetic methods including the synthesis under physiological conditions and creation of biodegradable nanocapsules. We then highlight unique properties of nanocapsules essential for practical applications, such as precise control of pore size and chemical environment, selective permeability, and ultrafast transport through the pores. We discuss new motifs for catch and release of small molecules with porous nanocapsules based on controlling the microenvironment inside the nanocapsules, regulating the charge on the orifice of nanopores in the shells, and reversible synergistic action of host and guest forming a supramolecular complex in nanocapsules. We demonstrate successful creation of fast-acting and selective nanoreactors by encapsulation of diverse homogeneous and nanoparticle catalysts. Due to unhindered flow of substrates and products through the nanopores, encapsulation did not compromise catalytic efficiency and, in fact, improved the stability of entrapped catalysts. We present robust nanoprobes based on nanocapsules with entrapped sensing agents and show how the encapsulation resulted in selective measurements with fast response times in challenging conditions, such as small volumes and complex mixtures. Throughout this Account, we highlight the advantages of encapsulation and discuss the opportunities for future design of nanodevices.

Vesicle-templated nanocapsules are prepared by polymerization of hydrophobic acrylic monomers and cross-linkers in the hydrophobic interior of self-assembled bilayers. Understanding the mechanism of capsule formation and the influence of synthetic parameters on the structural features and functional performance of nanocapsules is critical for the rational design of functional nanodevices, an emerging trend of application of the nanocapsule platform. This study investigated the relationship between basic parameters of the formulation and synthesis of nanocapsules and structural and functional characteristics of the resulting structures. Variations in the monomer/surfactant ratio, temperature of polymerization, and the molar fraction of the free-radical initiators were investigated with a multipronged approach, including shell thickness measurements using small-angle neutron scattering, evaluation of the structural integrity of nanocapsules with scanning electron microscopy, and determination of the retention of entrapped molecules using absorbance and fluorescence spectroscopy. Surprisingly, the thickness of the shells did not correlate with the monomer/surfactant ratio, supporting the hypothesis of substantial stabilization of the surfactant bilayer with loaded monomers. Decreasing the temperature of polymerization had no effect on the spherical structure of nanocapsules but resulted in progressively lower retention of entrapped molecules, suggesting that a spherical skeleton of nanocapsule forms rapidly, followed by filling the gaps to create the structure without pinholes. Lower content of initiators resulted in slower reactions, outlining the baseline conditions for practical synthetic protocols. Taken together, these findings provide insights into the formation of nanocapsules and offer methods for controlling the properties of nanocapsules in viable synthetic methods.

Nanocapsules with molecules threaded through the porous shells may lead to advanced cell-mimicking functional devices. Herein, we show the feasibility of synthesizing such hybrid nanostructures by using vesicle-templated polymer nanocapsules with controlled nanopores. Ship-in-a-bottle assembly inside a nanocapsule created an internal unit. An external unit was then connected to an entrapped internal unit through pre-attached linker threaded through a nanopore in the shell of the nanocapsule. Both internal and external units are larger than the pore size and cannot cross the shell, producing a rotaxane-like structure. Successful synthesis was achieved with fairly short linkers (six and ten carbon atoms in a chain), creating an opportunity for facile synthesis of functional devices capable of cross-shell communication.

Ground-state atomic oxygen [O(3P)] is an oxidant whose formation in solution was proposed but never proven. Polymer nanocapsules were used to physically separate dibenzothiophene S-oxide (DBTO), a source of O(3P), from an O(3P)-accepting molecule. Irradiation of polymer nanocapsules loaded with DBTO resulted in oxidation of the O(3P)-acceptor placed outside nanocapsules. The results rule out a direct oxygen atom transfer mechanism and are consistent with freely diffusing O(3P) as the oxidant.

Yolk-shell nanoreactors with metal nanoparticle core and ultrathin porous polymer shells are effective catalysts for heterogeneous reactions. Polymer shells provide size-selectivity and improved reusability of catalyst. Nanocapsules with single-nanometer porous shells are prepared by vesicle-templated directed assembly. Metal nanoparticles are formed either by selective initiation in pre-fabricated nanocapsules or simultaneously with the creation of a crosslinked polymer shell. In this study, we investigated the oxidation of benzyl alcohol and benzaldehyde catalyzed by gold nanoparticles and hydrogenation of cyclohexene catalyzed by platinum nanoparticles. Comparison of newly created nanoreactors with commercially available nanoparticles revealed superior reusability and size selectivity in nanoreactors while showing no negative effect on reaction kinetics.

To develop simple optical pH sensors with adequate sensitivity, short response time, and extended life time for the analysis of very small sample volumes, high concentrations of pH sensitive indicator dyes were encapsulated into ∼200 nm diameter nanocapsules (NCs) with ∼1 nm thick porous walls. The capsules were immobilized into high-porosity polyvinyl alcohol (PVA) gels for robust and versatile sensor platform design (double immobilization). The NCs-loaded gels were molded into sensing cylinders and secured in glass capillaries, which served as sampling devices and flow-through optical detector cells (capillary optodes). The color of the sensing cylinder was measured as a function of the sample pH using an optical fiber-based UV-VIS spectrophotometer. To optimize the optical properties of the sensing gel the influence of the size of the NCs, the dye concentration in the NCs and the NCs concentration within the PVA gel were studied. The NCs-based optodes allowed the measurement of the pH within 2 minutes in as little as ∼30 µL volume of sample, with ∼±0.03 pH unit uncertainty and less than 0.001 pH/hour drift.

Vesicle-templated nanocapsules have emerged as a viable platform for diverse applications. Shell thickness is a critical structural parameter of nanocapsules, where the shell plays a crucial role providing mechanical stability and control of permeability. Here we used small-angle neutron scattering (SANS) to determine the thickness of freestanding and surfactant-stabilized nanocapsules. Despite being at the edge of detectability, we were able to show the polymer shell thickness to be typically 1.0 ± 0.1 nm, which places vesicle-templated nanocapsules among the thinnest materials ever created. The extreme thinness of the shells has implications for several areas: mass-transport through nanopores is relatively unimpeded; pore-forming molecules are not limited to those spanning the entire bilayer; the internal volume of the capsules is maximized; and insight has been gained on how polymerization occurs in the confined geometry of a bilayer scaffold, being predominantly located at the phase-separated layer of monomers and cross-linkers between the surfactant leaflets.

This work addresses the challenge of creating hollow nanocapsules with a controlled quantity of encapsulated molecules. Such nanocontainers or nanorattle-like structures represent an attractive platform for building functional devices, including nanoreactors and nanosensors. By taking advantage of the electrostatic attraction between oppositely charged cargo molecules and the surface of the templating bilayer of catanionic vesicles, formed by mixing single-tailed cationic and anionic surfactants, we were able to achieve a substantial increase in the local concentration of molecules inside the vesicle-templated nanocapsules. Control of electrostatic interactions through changes in the formulation of catanionic vesicles or the pH of the solution enabled fine tuning of the encapsulation efficiency in capturing ionic solutes. The ability to control the quantity of entrapped molecules greatly expands the application of nanocontainers in the creation of functional nanodevices.

We have developed a novel design of optical nanothermometers that can measure the surrounding temperature in the range of 20–85°C. The nanothermometers comprise of two organic fluorophores encapsulated in a crosslinked polymethacrylate nanoshell. The role of the nanocapsule shell around the fluorophores is to form a well-defined and stable microenvironment to prevent other factors besides temperature from affecting the dyes’ fluorescence. The two fluorophores feature different temperature-dependent emission profiles where a fluorophore with relatively insensitive fluorescence (rhodamine 640) serves as a reference while a sensitive fluorophore (indocyanine green) serves as a sensor. The sensitivity of the nanothermometers depends on the type of nanocapsules-forming lipid and is affected by the phase transition temperature. Both the fluorescence intensity and the fluorescence lifetime can be utilized to measure the temperature.

Self-assembled gold monolayers offer several advantages for the realization of novel modified electrodes for biosensor applications. This is due to their ability to decrease non-specific adsorption and provide for covalent attachment of biomolecules. Surfaces for these applications require the precise control of ligand density, the ability to immobilize ligands, and in situ-modulation of ligand activity. In this study, we focused our studies on the immobilization of antibody on a gold monolayer surface. We self-assembled thioctic acid onto the gold surface as an anchor point for the immobilization of anti-fibrinogen onto the surface. The modifications to the gold surface were characterized by ELISA, ellipsometry, and AFM.

Large molecules can be assembled from small components exclusively inside hollow nanocapsules with the help of entrapped catalysts. Phenyl isocyanates enter the capsules through nanopores in the capsule shells and form cyclic trimers that remain entrapped. No assembly happens outside the nanocapsules. Further functionalization of trimers produces functional hierarchical nanomaterials.

Yolk–shell nanostructures, or nanorattles, are created by growing metal nanoparticles exclusively inside hollow porous polymer nanocapsules. Metal ions enter the nanocapsules through size-selective nanopores. Synthesis of metal nanoparticles is initiated by an agent entrapped in nanocapsules. Tannic acid, β-cyclodextrin, and polyether dendrimer were used as sacrificial molecules for initiation and growth of gold nanoparticles. If needed, initiator molecules can be fragmented by acid hydrolysis and removed from nanocapsules. Variations in reaction conditions yield encapsulated nanoparticles with different size and shape. Further functionalization of nanorattles forms encapsulated core–shell nanoparticles.

Nanoprobes for surface-enhanced Raman scattering (SERS) were prepared by creating nanorattles, or yolk−shell structures, containing gold or silver nanoparticles entrapped in porous hollow polymer nanocapsules. Controlled permeability of the shells of nanocapsules, achieved by controlling the pore size and/or shell surface functionalization, resulted in size- and charge-selective SERS analyses. For example, a trace amount of phenanthroline, a model analyte, was detected in human blood plasma without preprocessing of plasma samples. Comparison with commercially available nanoparticles showed superior performance of the newly prepared nanorattle structures.

Gold nanoparticles entrapped in the hollow polymer nanocapsules undergo pH-mediated controlled aggregation. Encapsulated clusters of nanoparticles show absorbance at higher wavelengths compared with individual nanoparticles. The size of the aggregates is controlled by the number of nanoparticles entrapped in individual nanocapsules. Such controlled aggregation may permit small biocompatible nanoparticles exhibit desirable properties for biomedical applications that are typically characteristic of large nanoparticles.

We designed new terpolymers responsive to pH, temperature, and metal ions. Binding of metal ions amplifies the magnitude of thermal response. Variations in the pH and concentration of metal ions enable tuning the lower critical solution temperature (LCST) and thermosensitivity in a broad range. Upon changes in pH and/or temperature, polymers form associates with narrow size distribution ranging from less than 5 nm to more than 250 nm in diameter. The multistimuli-responsive properties of newly synthesized polymers are the result of combining hydrophobic, ionogenic, and non-charged hydrophilic moieties within the terpolymer structure. Polymers are produced by a potentially scalable method from inexpensive starting materials, 2-hydroxyethylacrylate (HEA), butylmethacrylate (BMA), and acrylic acid (AA). Polymers and their aggregates are characterized by NMR, dynamic light scattering, and electron microscopy. The ability to control the size of polymer aggregates and the magnitude of response to external stimuli opens exciting opportunities for practical applications.

Plasticized PVC membrane-based potassium or sodium ion-selective optodes were incorporated into sampling capillaries in combination with sol-gel-based hydrogen ion-selective optodes for the sampling and analysis of minute tear fluid samples. The performance characteristic of the K+/pH and Na+/pH sensor arrays were optimized for an adequate dynamic response range, sensitivity, stability, and response time. The precision and accuracy of the combined sampling/measurement system was evaluated both in stopped flow and continuous flow modes using aqueous standard solutions. By using a two point calibration protocol, with pH standards bracketing the sample, the pH of 20 µL pooled human tear samples could be determined with a precision less than ±0.03 pH units. Errors in the pH measurements have a significant influence on the attainable precision and accuracy of the ion-exchange-based K+ and Na+ optodes. Nevertheless, the results of the quantitative assessment of the K+ and Na+ concentrations in “check” standards and pooled human tear fluid samples were within ±5 % of the nominal values or of the results of the determinations with atomic absorption spectrophotometry. Cationic surfactants in artificial tear drops were found to interfere with the K+ and Na+ optode responses. No interference was detected in the presence of anionic and nonionic surfactants.

We describe a new co-entrapment and release motif based on the combination of noncovalent and steric interactions in materials with well-defined nanopores. Individual components enter hollow nanocapsules through nanopores in the capsule shell. Their complex, larger than the pore size, remains entrapped. The dissociation of the complex upon external stimulus releases entrapped components. Reversible formation of complexes between diaza-18-crown-6 and metal ions was used to demonstrate the feasibility of new approach to co-entrapment and triggered release.

Cross-linked polystyrene nanodisks were prepared by controlled polymerization of styrene and divinylbenzene in the interior of bicelles, discoidal lipid aggregates. Aggregation behavior of polymer nanodisks was studied in water, organic solvents, and solid phase. Nanodisks form stable dispersions in aqueous solutions of surfactants, such as sodium dodecyl sulfate (SDS). Varying SDS/nanodisk ratio allowed us to control the size of nanodisk aggregates. Nanodisks are readily solubilized in nonpolar organic solvents, such as toluene and carbon tetrachloride, to yield stable monodisperse suspensions. These findings open opportunities for creating nanodisk-based nanocomposite materials. Stable nanodisk suspension in toluene enabled small angle neutron scattering (SANS) measurements. SANS data confirmed the nanodisk diameter and allowed accurate measurement of nanodisk thickness (19.5 ± 1.0 A). In solid phase, nanodisks aggregate in sub-micron platelets.

Hydrophobic monomers partially phase separate from saturated lipids when loaded into lipid bilayers in amounts exceeding a 1:1 monomer/lipid molar ratio. This conclusion is based on the agreement between two independent methods of examining the structure of monomer-loaded bilayers. Complete phase separation of monomers from lipids would result in an increase in bilayer thickness and a slight increase in the diameter of liposomes. A homogeneous distribution of monomers within the bilayer would not change the bilayer thickness and would lead to an increase in the liposome diameter. The increase in bilayer thickness, measured by the combination of small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS), was approximately half of what was predicted for complete phase separation. The increase in liposome diameter, measured by dynamic light scattering (DLS), was intermediate between values predicted for a homogeneous distribution and complete phase separation. Combined SANS, SAXS, and DLS data suggest that at a 1.2 monomer/lipid ratio approximately half of the monomers are located in an interstitial layer sandwiched between lipid sheets. These results expand our understanding of using self-assembled bilayers as scaffolds for the directed covalent assembly of organic nanomaterials. In particular, the partial phase separation of monomers from lipids corroborates the successful creation of nanothin polymer materials with uniform imprinted nanopores. Pore-forming templates do not need to span the lipid bilayer to create a pore in the bilayer-templated films.

Hollow polymer nanocapsules are produced by the polymerization within hydrophobic interior of lipid bilayers that act as temporary self-assembled scaffolds. Pore-forming templates are co-dissolved with monomers in the bilayers to create pores with controlled size and chemical environment. Polymerization was monitored with UV spectroscopy and dynamic light scattering. High resolution magic angle spinning NMR characterization provided detailed structural information about nanocapsules. Spherical shape was confirmed by electron microscopy. Medium-sized molecules can be entrapped within porous nanocapsules. No release of encapsulated molecules was observed within 240 days.

Robust surface-bound insulating polymer films with controlled thickness in

Directed assembly of nanostructures within temporary and recyclable self-assembled scaffolds is emerging as an attractive method for the synthesis of nanomaterials with programmed properties. Understanding interactions of building blocks with amphiphilic scaffolds is critical for rational design of new nanostructures and nanodevices. Here we examine loading of hydrophobic monomers into bilayers with different curvatures. Time-resolved loading was studied by high performance liquid chromatography and dynamic light scattering. Despite differences in initial bilayer geometry, loading rates and maximum bilayer capacity are the same for liposomes with radii ranging from 25 to 100 nm. When using divinylbenzene (DVB) and dimyristoylphosphatidylcholine (DMPC), monomer/lipid loading ratio of 1.2 was achieved within 12 hours. While accommodation of a large amount of monomers is likely to be accompanied with significant changes in bilayer structure, all liposomes in this study including those with smallest size and higher bilayer curvature retain encapsulated content and show no evidence of fusion during monomer loading. These results contribute to our understanding of interactions between hydrophobic molecules and lipid bilayers and expand the scope of the directed assembly method.

Using temporary self-assembled scaffolds to preorganize building blocks is a potentially powerful method for the synthesis of organic nanostructures with programmed shapes. We examined the underlying phenomena governing the loading of hydrophobic monomers into lipid bilayer interior and demonstrated successful control of the amount and ratio of loaded monomers. When excess styrene derivatives or acrylates were added to the aqueous solution of unilamellar liposomes made from saturated phospholipids, most loading occurs within the first few hours. Dynamic light scattering and transmission electron microscopy revealed no evidence of aggregation caused by monomers. Bilayers appeared to have a certain capacity for accommodating monomers. The total volume of loaded monomers is independent of monomer structure. X-ray scattering showed the increase in bilayer thickness consistent with loading monomers into bilayer interior. Loading kinetics is inversely proportional to the hydrophobicity and size of monomers. Loading and extraction kinetic data suggest that crossing the polar heads region is the rate limiting step. Consideration of loading kinetics and multiple equilibria are important for achieving reproducible monomer loading. The total amount of monomers loaded into the bilayer can be controlled by the loading time or length of hydrophobic lipid tails. The ratio of loaded monomers can be varied by changing the ratio of monomers used for loading or by the time-controlled replacement of a preloaded monomer. Understanding and controlling the loading of monomers into bilayers contributes to the directed assembly of organic nanostructures.

ATP release from erythrocytes in response to low oxygen tension requires an increase in cAMP, the level of which is regulated by phosphodiesterase 3 (PDE3). Such release is defective in erythrocytes of humans with type 2 diabetes (DM2). This study tested a hypothesis that direct delivery of the clinically useful PDE3 inhibitor, cilostazol, to erythrocytes of humans with type 2 diabetes using liposomes would restore low-oxygen tension-induced ATP release. Cilostazol was incorporated into liposomes prepared from dimyristoylphosphatidylcholine (DMPC). Liposome-delivery of cilostazol restored ATP release from DM2 erythrocytes to levels which were not different from that released from non-cilostazol treated healthy erythrocytes under the same conditions. There were no observed adverse effects of the liposomes on either healthy or DM2 erythrocytes. The directed liposomal delivery of PDE inhibitors to erythrocytes may help prevent or slow the development of peripheral vascular disease in individuals with DM2 by restoring an important physiological controller of microvascular perfusion while minimizing side effects associated with systemic delivery of some of these inhibitors., Graphical abstract, Highlights • Liposomes can deliver phosphodiesterase (PDE) inhibitors to erythrocytes. • No adverse effect of drug-loaded liposomes on erythrocytes was observed. • Release of ATP from erythrocytes of patients with type 2 diabetes was investigated. • Liposome-delivered PDE inhibitors restore the release of ATP in response to low O2.

This work addresses the challenge of creating hollow polymer capsules with wall thickness in the single-nanometer range under mild conditions. We present a simple and scalable method for the synthesis of hollow polymer nanocapsules in the bilayers of spontaneously assembled surfactant vesicles. Polymerization is initiated thermally with the help of a peroxide initiator and an amine activator codissolved with monomers and cross-linkers in the hydrophobic interior of the surfactant bilayer. To avoid premature polymerization, the initiator and the activator were added separately to the mixtures of cetyltrimethylammonium tosylate (CTAT) and sodium dodecylbenzenesulfonate (SDBS) containing monomers and cross-linkers. Upon hydration and mixing of the aqueous solutions, equilibrium monomer-loaded vesicles formed spontaneously after a brief incubation. The removal of oxygen and further incubation at slightly elevated temperatures (35-40 °C) for 1 to 2 h has led to the formation of hollow polymer nanocapsules. Structural and permeability characterization supported the high yield of nanocapsules with no pinhole defects.

Osteoarthritis (OA) is a major cause of pain and disability in the US. A problem with early intervention is that it is very difficult to detect OA before irreversible damage has already occurred. This study characterizes a novel method of early OA detection in a mouse model of post-traumatic osteoarthritis (PTOA) using fluorescent nanosomes. In this investigation, knee injury was induced in mice by compressive loading. Nanosomes encapsulating fluorescent dye and conjugated to collagen type II antibody were utilized to detect cartilage damage in vivo. Cartilage damage and OA progression were detected by the use of fluorescence-imaging (IVIS) and histopathology. Histopathology analyses showed that mild osteoarthritic changes had occurred. This corresponded with a higher fluorescence on IVIS imaging due to more nanosome binding. These results suggest that theragnostic nanosomes may be useful for detection of early PTOA as well as for targeted delivery of interventional agents. From the Clinical Editor With the aging population, osteoarthritis now poses a significant problem worldwide. Early detection may help slow the progression of the disease. In this study, the authors described the use of fluorescent nanosomes to detect early cartilage damage in a mouse model of osteoarthritis. This detection method may also prove to be useful for targeted delivery of drugs in the future.

Complexation of p-tert-butylcalix[4]arene derivatives with a series of neutral guests in CCl4 solution was studied. The formation of inclusion-type complexes was determined. The solution structural data obtained were compared with solid state (X-ray) data and with the results of AMBER force field calculations for several compounds. Stability constants were measured by the conventional NMR titration technique. The relationship of the nature of the guest and substitution pattern in the calix[4]arene lower rim with the complex stabilities is discussed.

Here, we show that the charge of the nanopores in the nanometer-thin shells of hollow porous nanocapsules can regulate the transport of charged molecules. By changing the pH of external aqueous solution, we can entrap charged molecules in nanocapsules and trigger the release of encapsulated content.

Surfactant vesicles containing monomers in the interior of the bilayer were used to template hollow polymer nanocapsules. This study investigated the formation of surfactant/monomer assemblies by two loading methods, concurrent loading and diffusion loading. The assembly process and the resulting aggregates were investigated with dynamic light scattering, small angle neutron scattering, and small-angle X-ray scattering. Acrylic monomers formed vesicles with a mixture of cationic and anionic surfactants in a broad range of surfactant ratios. Regions with predominant formation of vesicles were broader for compositions containing acrylic monomers compared with blank surfactants. This observation supports the stabilization of the vesicular structure by acrylic monomers. Diffusion loading produced monomer-loaded vesicles unless vesicles were composed from surfactants at the ratios close to the boundary of a vesicular phase region on a phase diagram. Both concurrent-loaded and diffusion-loaded surfactant/monomer vesicles produced hollow polymer nanocapsules upon the polymerization of monomers in the bilayer followed by removal of surfactant scaffolds.

Surfactants and hydrophobic monomers spontaneously assemble into vesicles containing monomers within the bilayer. The joint action of monomers and surfactants is essential in this synergistic self-assembly. Polymerization in the bilayer formed hollow polymer nanocapsules.

Calix[4]arene derivatives are used as a scaffold for the attachment of chiral substituents. Calix[4]arenes having either lower or upper rim capped with chiral binaphtholic species 5 and 6, as well as new biscalix[4]arenodiaza-18-crown-6 (8), have been synthesized.

Although there have been substantial advancements in the treatment of inflammatory arthritis, treatments for osteoarthritis (OA) have lagged and currently are primarily palliative until joints become totally dysfunctional and prosthetic replacement is needed. One obstacle for developing a preventive therapy for OA is the lack of good tools for efficiently diagnosing the disease and monitoring its progression during the early stages when the effect of therapeutic drugs or biologics is most likely to be effective. We have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA. These immunoliposomes bind to damaged but not normal cartilage. Utilizing these reagents, we can quantitate exposure of type II collagen during cartilage degradation in individual joints in vivo in a guinea pig. Immunoliposomes could be used to determine the effectiveness of therapeutic interventions in small animals as well as vehicles for localized drug delivery to OA chondrocytes. From the Clinical Editor This team of authors have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA, with promising results demonstrated in a guinea pig model.

In this work we report on a versatile sensor platform based on encapsulated indicator dyes. Dyes are entrapped in hollow nanocapsules with nanometer-thin walls of controlled porosity. The porous nanocapsules retain molecules larger than the pore size but provide ultrafast access to their interior for molecules and ions smaller than the pore size. Dye-loaded nanocapsules are immobilized in a polyvinyl alcohol (PVA) matrix with high solvent permeability and rapid analyte diffusion. This approach provides robust sensing films with fast response and extended lifetime. To demonstrate the performance characteristics of such films, pH-sensitive indicator dyes were entrapped in vesicle-templated nanocapsules prepared by copolymerization of tert-butyl methacrylate, butyl methacrylate, and ethylene glycol dimethacrylate. As pH sensitive dyes, Nile blue A, bromophenol blue, and acid fuchsin were tested. Time-resolved absorbance measurements showed that the rate of the color change is controlled by the rate of diffusion of protons in the hydrogel. The pH-induced color change in a ~400 μm thick film is complete within 40 and 60 s. The porous nanocapsule loaded films showed excellent stability and reproducibility in long-term monitoring experiments. Compartmentalization of the indicator dyes within the nanocapsules increased their stability. The matrix caused a shift in the position of the color change of the dye compared to that in an aqueous buffer solution. The encapsulation/immobilization protocol described in this account is expected to be broadly applicable to a variety of indicator dyes in optical sensor applications.

Polymeric nanocapsules with nanometre-thin walls offer a promising platform for controlled cellular delivery of therapeutic or diagnostic agents. Therefore, their biocompatibility is crucial for future applications in the human body. However, there is little knowledge about their interaction with biological systems. In this study, polymeric nanocapsules containing different amounts of lipids and representing different scenarios for handling and storing nanocapsules are investigated. We find that all nanocapsules in our study can enter human cells and the presence of an outer lipid shell facilitates the process. These nanocapsules do not inhibit cell proliferation at concentrations up to 200 μg mL(-1) of nanocapsules. No cellular ROS, apoptosis or cell cycle perturbation is detected at this dose. These comprehensive examinations demonstrate that polymeric nanocapsules are promising nano-carriers for cellular delivery.

Calix[4]arene derivatives are used as a scaffold for the attachment of chiral substituents. Calix[4]arenes having either lower or upper rim capped with chiral binaphtholic species 5 and 6 , as well as new biscalix[4]arenodiaza-18-crown-6 ( 8 ), have been synthesized.

Nanometre-thin membranes, prepared by directed assembly within lipid bilayers, are capable of unhindered transport of ions while being impermeable to medium sized molecules.

A series of aminophosphonates was synthesized, and their ability to carry alanine, a model hydrophilic molecule, across phospholipid bilayer membranes was evaluated. Aminophosphonates facilitate the membrane transport at moderate rates, which make them a suitable platform for the design of carriers for continuous drug release devices.

Rapid-release drug delivery systems present a new paradigm in emergency care treatments. Such systems combine a long shelf life with the ability to provide a significant dose of the drug to the bloodstream in the shortest period of time. Until now, development of delivery formulations has concentrated on slow release systems to ensure a steady concentration of the drug. To address the need for a quick release system, we created hollow polyacrylate nanocapsules with nanometer-thin porous walls. Burst release occurs upon interaction with blood components that leads to escape of the cargo. The likely mechanism of release involves a conformational change of the polymer shell caused by binding albumin. To demonstrate this concept, a near-infrared fluorescent dye indocyanine green (ICG) was incorporated inside the nanocapsules (NCs). ICG-loaded nanocapsules demonstrated a remarkable shelf life in aqueous buffers with no release of ICG for twelve months. Rapid release of the dye was demonstrated first in vitro using albumin solution and serum. SEM and light scattering analysis demonstrated the retention of the nanocapsule architecture after the release of the dye upon contact with albumin. In vivo studies using fluorescence lifetime imaging confirmed quick discharge of ICG from the nanocapsules following intravenous injection.