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Implantable drug depots have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential systemic side effects. Tubular organs including the gastrointestinal tract, respiratory tract and vasculature all manifest with endoluminal disease. The anatomic distribution of localized drug delivery for these organs using existing therapeutic modalities is limited. Application of local depots in a circumferential and extended longitudinal fashion could transform our capacity to offer effective treatment across a range of conditions. Here we report the development and application of a kirigami-based stent platform to achieve this. The stents comprise a stretchable snake-skin-inspired kirigami shell integrated with a fluidically driven linear soft actuator. They have the capacity to deposit drug depots circumferentially and longitudinally in the tubular mucosa of the gastrointestinal tract across millimetre to multi-centimetre length scales, as well as in the vasculature and large airways. We characterize the mechanics of kirigami stents for injection, and their capacity to engage tissue in a controlled manner and deposit degradable microparticles loaded with therapeutics by evaluating these systems ex vivo and in vivo in swine. We anticipate such systems could be applied for a range of endoluminal diseases by simplifying dosing regimens while maximizing drug on-target effects through the sustained release of therapeutics and minimizing systemic side effects. A kirigami-inspired stent-based system has been developed for extended local drug delivery to the gastrointestinal and respiratory tracts as well as the vascular system.

Continuous monitoring in the intensive care setting has transformed the capacity to rapidly respond with interventions for patients in extremis. Noninvasive monitoring has generally been limited to transdermal or intravascular systems coupled to transducers including oxygen saturation or pressure. Here it is hypothesized that gastric fluid (GF) and gases, accessible through nasogastric (NG) tubes, commonly found in intensive care settings, can provide continuous access to a broad range of biomarkers. A broad characterization of biomarkers in swine GF coupled to time‐matched serum is conducted . The relationship and kinetics of GF‐derived analyte level dynamics is established by correlating these to serum levels in an acute renal failure and an inducible stress model performed in swine. The ability to monitor ketone levels and an inhaled anaesthetic agent (isoflurane) in vivo is demonstrated with novel NG‐compatible sensor systems in swine. Gastric access remains a main stay in the care of the critically ill patient, and here the potential is established to harness this establishes route for analyte evaluation for clinical management., Nasogastric tube placement in intensive care settings is a mainstay in the management of critical conditions. The authors demonstrate that systemic biomarkers are present in gastric fluid and that nasogastric tubes can be leveraged to monitor systemic disturbances through evaluation of these biomarkers. Real‐time biomarker monitoring can help improve responsiveness of clinical teams and improve critical care.

A one-pot soft-templating method is reported to fabricate nanosized bimetallic PdAg hollow mesoporous nanospheres (HMSs) for electrocatalytic ethanol oxidation reaction (EOR). The synthesis relies on the "dual-template" surfactant of dioctadecyldimethylammonium chloride that drives in situ growth of mesoporous frameworks on the surface of vesicles into the HMSs with radially opened mesochannels. The synthetic protocol is extendable to engineer elemental compositions and hierarchical nanostructures of PdAg nanoalloys. This system thus provides a direct yet solid platform to understand catalytic add-in synergies of PdAg HMSs toward electrochemical EOR. By evaluating compositional and structural features separately, bimetallic Pd65Ag35 HMSs display the highest EOR activity with a mass activity of 4.61 A mgPd-1. Mechanism studies indicate that synergistically electronic and bifunctional effects as well as structural advantages of Pd65Ag35 HMSs kinetically optimize the removal of poisoning carbonaceous intermediates and accelerate the diffusion processes (the rate-determining step), and thus promote the EOR performance accordingly.

Mesoporous colloidal nanospheres with tailorable asymmetric nanostructures and multimetallic elemental compositions are building blocks in next-generation heterogeneous catalysts. Introducing structural asymmetry into metallic mesoporous frameworks has never been demonstrated, but it would be beneficial because the asymmetry enables the spatial control of catalytic interfaces, facilitates the electron/mass transfer and assists in the removal of poisonous intermediates. Herein, we describe a simple bottom-up strategy to generate uniform sub-100 nm multimetallic asymmetric bowl-shaped mesoporous nanospheres (BMSs). This method uses a surfactant-directed "dual"-template to control the kinetics of metal reduction on the surface of a vesicle, forming mesoporous metal islands on its surface whose spherical cone angle can be precisely controlled. The asymmetric BMS mesostructures with different spherical cone angles (structural asymmetries) and elemental compositions are demonstrated. The high surface area and asymmetric nature of the metal surfaces are shown to enhance catalytic performance in the alcohol oxidation reactions. The findings described here offer novel and interesting opportunities for rational design and synthesis of hierarchically asymmetric nanostructures with desired functions for a wide range of applications.

Au is one of the most promising electrocatalysts to convert CO2 into CO in an aqueous-phase electrochemical reduction. However, ultrasmall Au nanocatalysts (AuNCs

A general synthetic methodology is reported to grow ultrafine cobalt-based nanoparticles (NPs, 2–7 nm) within high-surface-area mesoporous carbon (MC) frameworks. Our design strategy is based on colloidal amphiphile (CAM) templated oxidative self-polymerization of dopamine. The CAM templates consisting of a hydrophobic silica-like core and a hydrophilic PEO shell can coassemble with dopamine and template its self-polymerization to form polydopamine (PDA) nanospheres. Given that PDA has rich binding sites such as catechol and amine to coordinate metal ions (e.g., Co2+), PDA nanospheres containing Co2+ ions can be converted into hierarchical porous carbon frameworks containing ultrafine metallic Co NPs (Co@MC) using high-temperature pyrolysis. The CAM templates offer strong “nanoconfinements” to prevent the overgrowth of Co NPs within carbon frameworks. The yielded ultrafine Co NPs have an average size of

Nanoformulations are transforming our capacity to effectively deliver and treat a myriad of conditions. However, many nanoformulation approaches still suffer from high production complexity and low drug loading. One potential solution relies on harnessing co-assembly of drugs and small molecular excipients to facilitate nanoparticle formation through solvent exchange without the need for chemical synthesis, generating nanoparticles with up to 95% drug loading. However, there is currently no understanding which of the millions of possible combinations of small molecules can result in the formation of these nanoparticles. Here we report the development of a high-throughput screening platform coupled to machine learning to enable the rapid evaluation of such nanoformulations. Our platform identified 101 novel self-assembling drug nanoparticles from 2.1 million pairings derived from 788 candidate drugs with one of 2686 excipients, spanning treatments for multiple diseases and often harnessing well-known food additives, vitamins, or approved drugs as carrier materials – with potential for accelerated approval and translation. Given their long-term stability and potential for clinical impact, we further characterize novel sorafenib-glycyrrhizin and terbinafine-taurocholic acid nanoparticles ex vivo and in vivo. We anticipate that this platform could accelerate the development of safer and more efficacious nanoformulations with high drug loadings for a wide range of therapeutics.

New synthetic methods capable of controlling structural and compositional complexities of asymmetric nanoparticles (NPs) are very challenging but highly desired. A simple and general synthetic approach to designing sophisticated asymmetric NPs by anisotropically patterning the surface of isotropic metallic NPs with amphiphilic block copolymers (BCPs) is reported. The selective galvanic replacement and seed-mediated growth of a second metal can be achieved on the exposed surface of metal NPs, resulting in the formation of nanobowls and Janus-type metal-metal dimers, respectively. Using Ag and Au NPs tethered with amphiphilic block copolymers of poly(ethylene oxide)-block-polystyrene (PEO-b-PS), anisotropic surface patterning of metallic NPs (e.g., Ag and Au) is shown to be driven by thermodynamical phase segregation of BCP ligands on isotropic metal NPs. Two proof-of-concept experiments are given on, i) synthesis of Au nanobowls by a selective galvanic replacement reaction on Janus-type patched Ag/polymer NPs; and ii) preparation of Au-Pd heterodimers and Au-Au homodimers by a seed-mediated growth on Janus-type patched Au/polymer NPs. The method shows remarkable versatility; and it can be easily handled in aqueous solution. This synthetic strategy stands out as the new methodology to design and synthesis asymmetric metal NPs with sophisticated topologies.