Tuning Ligand Density To Optimize Pharmacokinetics of Targeted Nanoparticles for Dual Protection against Tumor-Induced Bone Destruction.

Breast cancer patients are at high risk for bone metastasis. Metastatic bone disease is a major clinical problem that leads to a reduction in mobility, increased risk of pathologic fracture, severe bone pain, and other skeletal-related events. The transcription factor Gli2 drives expression of parathyroid hormone-related protein (PTHrP), which activates osteoclast-mediated bone destruction, and previous studies showed that Gli2 genetic repression in bone-metastatic tumor cells significantly reduces tumor-induced bone destruction. Small molecule inhibitors of Gli2 have been identified; however, the lipophilicity and poor pharmacokinetic profile of these compounds have precluded their success in vivo. In this study, we designed a bone-targeted nanoparticle (BTNP) comprising an amphiphilic diblock copolymer of poly[(propylene sulfide)-block-(alendronate acrylamide-co-N,N-dimethylacrylamide)] [PPS-b-P(Aln-co-DMA)] to encapsulate and preferentially deliver a small molecule Gli2 inhibitor, GANT58, to bone-associated tumors. The mol % of the bisphosphonate Aln in the hydrophilic polymer block was varied in order to optimize BTNP targeting to tumor-associated bone by a combination of nonspecific tumor accumulation (presumably through the enhanced permeation and retention effect) and active bone binding. Although 100% functionalization with Aln created BTNPs with strong bone binding, these BTNPs had highly negative zeta-potential, resulting in shorter circulation time, greater liver uptake, and less distribution to metastatic tumors in bone. However, 10 mol % of Aln in the hydrophilic block generated a formulation with a favorable balance of systemic pharmacokinetics and bone binding, providing the highest bone/liver biodistribution ratio among formulations tested. In an intracardiac tumor cell injection model of breast cancer bone metastasis, treatment with the lead candidate GANT58-BTNP formulation decreased tumor-associated bone lesion area 3-fold and increased bone volume fraction in the tibiae of the mice 2.5-fold. Aln conferred bone targeting to the GANT58-BTNPs, which increased GANT58 concentration in the tumor-associated bone relative to untargeted NPs, and also provided benefit through the direct antiresorptive therapeutic function of Aln. The dual benefit of the Aln in the BTNPs was supported by the observations that drug-free Aln-containing BTNPs improved bone volume fraction in bone-tumor-bearing mice, while GANT58-BTNPs created better therapeutic outcomes than both unloaded BTNPs and GANT58-loaded untargeted NPs. These findings suggest GANT58-BTNPs have potential to potently inhibit tumor-driven osteoclast activation and resultant bone destruction in patients with bone-associated tumor metastases.

Continuous Energy Harvesting and Motion Sensing from Flexible Electrochemical Nanogenerators: Toward Smart and Multifunctional Textiles.

Here, we demonstrate the utilization of biocompatible Prussian blue (PB) active coatings onto polyester-carbon nanotube (CNT) threads to enable a fiber-based platform for both power harvesting and continuous motion sensing. First, we show experimental evidence supporting that the mechanistic power generating mechanical-electrochemical coupling in an electrochemical generator (ECG) is best achieved with K-ion insertion, in contrast to the expected preference for Li-ion insertion for batteries. We then construct KPB fibers and demonstrate power generation in an ECG device up to 3.8 µW/cm2 at low frequencies relevant to human motion in either an aqueous or polymer gel electrolyte media. Further, by stitching these yarns into gloves or arm sleeves, our results show the continuous monitoring of finger or arm motion, respectively, during slow and repetitive human motion. Overall, our work demonstrates an ECG platform that overcomes the performance and integration barriers toward combined textile integration and human motion sensing while leveraging common materials and understanding extending from alkali metal-ion batteries.

Hierarchically Structured CeO2 Catalyst Particles From Nanocellulose/Alginate Templates for Upgrading of Fast Pyrolysis Vapors.

Hierarchically structured porous materials often exhibit advantageous functionality for many applications including catalysts, adsorbents, and filtration systems. In this study, we report a facile approach to achieve hierarchically structured, porous cerium oxide (CeO2) catalyst particles using a templating method based on nanocellulose, a class of renewable, plant-derived nanomaterials. We demonstrate the catalyst performance benefits provided by this templating method in the context of Catalytic Fast Pyrolysis (CFP) which is a promising conversion technology to produce renewable fuel and chemical products from biomass and other types of organic waste. We show that variations in the porous structures imparted by this templating method may be achieved by modifying the content of cellulose nanofibrils, cellulose nanocrystals, and alginate in the templating suspensions. Nitrogen physisorption reveals that nearly 10-fold increases in surface area can be achieved using this method with respect to commercially available cerium oxide powder. Multiscale electron microscopy further verifies that bio-derived templating can alter the morphology of the catalyst nanostructure and tune the distribution of meso- and macro-porosity within the catalyst particles while maintaining CeO2 crystal structure. CFP experiments demonstrate that the templated catalysts display substantially higher activity on a gravimetric basis than their non-templated counterpart, and that variations in the catalyst architecture can impact the distribution of upgraded pyrolysis products. Finally, we demonstrate that the templating method described here may be extended to other materials derived from metal chlorides to achieve 3-dimensional networks of hierarchical porosity.

Superior Mesenteric Artery Syndrome Complicated by Gastric Mucosal Necrosis Following Congenital Scoliosis Surgery: A Case Report.

CASE: This is a report of severe superior mesenteric artery (SMA) syndrome in an 11-year-old girl with congenital scoliosis following posterior spinal fusion and segmental spinal instrumentation. This was complicated by gastric mucosal necrosis but resolved satisfactory with prolonged nasogastric suction, intravenous fluids, and total parental nutrition. CONCLUSIONS: All pediatric spine surgeons should be aware of SMA syndrome following spine surgery. This case demonstrates that although rare, significant complications such as gastric mucosal necrosis can occur. When present, it can be treated successfully with prolonged conservative management. Comanagement with pediatric gastroenterology and pediatric general surgery is recommended.

Multifunctional Structural Ultrabattery Composite.

Here we demonstrate a composite material exhibiting dual multifunctional properties of a structural material and a redox-active battery. This incorporates three-dimensional aligned carbon nanotube interfaces that weave together a structural frame, redox-active battery materials, and a Kevlar-infiltrated solid electrolyte that facilitates ion transfer. Relative to the total measured composite material mass, we demonstrate energy density up to ∼1.4 Wh/kg, elastic modulus of 7 GPa, and tensile strength exceeding 0.27 GPa. Mechano-electrochemical analysis demonstrates stable battery operation under mechanical loading that validates multifunctional performance. These findings demonstrate how battery materials that are normally packaged under compression can be reorganized as elements in a structurally reinforced composite material.

High-rate potassium ion and sodium ion batteries by co-intercalation anodes and open framework cathodes.

Here we demonstrate a full-cell battery design that bridges the energy density and rate capability between that of supercapacitors or pseudocapacitors with that of traditional lithium-ion batteries. This is accomplished by pairing an anode that enables ultrafast ion co-intercalation, an open framework cathode that allows rapid ion diffusion, and linear ether based electrolyte that sustains cell-level stability and high rate performance. We show this platform to be suitable for both sodium and potassium batteries using graphite as the co-intercalation anode, and Prussian blue as the open framework cathode. Our devices exhibit active material energy densities >100 W h kg-1 with power density >1000 W kg-1 with cycling durability approaching ∼80% energy density retention over 2000 cycles. This work brings together state-of-the-art concepts for fast-charging batteries into a full-cell configuration.

Solvent mediated hybrid 2D materials: black phosphorus - graphene heterostructured building blocks assembled for sodium ion batteries.

Here we demonstrate the broad capability to exploit interactions at different length scales in 2D materials to prepare macroscopic functional materials containing hybrid black phosphorus/graphene (BP/G) heterostructured building blocks. First, heterostructured 2D building blocks are self-assembled during co-exfoliation in the solution phase based on electrostatic attraction of different 2D materials. Second, electrophoretic deposition is used as a tool to assemble these building blocks into macroscopic films containing these self-assembled 2D heterostructures. Characterization of deposits formed using this technique elucidates the presence of stacked and sandwiched 2D heterostructures, and zeta potential measurements confirm the mechanistic interactions driving this assembly. Building on the exceptional sodium alloying capacity of BP, these materials were demonstrated as superior binder-free and additive-free anodes for sodium batteries with specific discharge capacity of 2365 mA h gP-1 and long stable cycling duration. This study demonstrates how controllable co-processing of 2D materials can enable material control for stacking and building block assembly relevant to broad future applications of 2D materials.

Improving influenza vaccination rates for children through year-round scheduling.

OBJECTIVE: Barriers to influenza vaccination negatively impact immunization rates contributing to the morbidity and mortality from influenza. This study sought to determine if 1) the availability of year-round scheduling of annual autumn/winter influenza vaccination was associated with improved immunization rates for 2 high-risk populations of children and 2) this system was associated with early season vaccine administration. METHODS: A retrospective cohort analysis was utilized to compare immunization rates during the 2003-2004 and 2004-2005 seasons. Billing records were used to determine eligible patients and vaccine receipt. A single, pediatric practice was studied, and two groups of patients were analyzed: 1) infants aged 6-23 months and 2) children < 21 years old with asthma. As opposed to Year 1, in Year 2 appointments in "flu clinics" for the following autumn became available 7 months prior to when vaccine became available. Patients and providers could therefore schedule an immunization appointment throughout the year. RESULTS: In Year 1, 552/1365 (40.4%) infants received at least 1 dose of influenza vaccine compared to 940/1265 (74.3%) in Year 2 (p < 0.001). For patients with asthma, 309/1332 (23.2%) received at least 1 dose of vaccine in Year 1 compared with 522/1489 (35.1%) in Year 2 (p <0.001). Both groups also achieved higher immunization rates between September and November in Year 2 (p < 0.001). CONCLUSIONS: Year-round scheduling of influenza vaccination was associated with improved immunization rates in two high-risk populations, and may remove the barrier of scheduling difficulty, allow for a consistent year-round message from providers, and improve timing of vaccine administration.