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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS2013

Medicine Delivery Device with Integrated Sterilization and Detection

Sterile delivery devices can be created by integrating a medicine delivery instrument with surfaces that are coated with germicidal and anti-fouling material. This requires that a large-surface-area template be developed within a constrained volume to ensure good contact between the delivered medicine and the germicidal material. Both of these can be integrated using JPL-developed silicon nanotip or cryo-etch black silicon technologies with atomic layer deposition (ALD) coating of specific germicidal layers. The application of semiconductor processing techniques and technologies to the problems of fluid manipulation and delivery has enabled the integration of chemical, electrical, and mechanical manipulation of samples all within a single microfluidic device. This approach has been successfully applied at JPL to the automated processing, detection, and analysis of minute quantities (parts per trillion level) of biomaterials to develop instruments for in situ exploration or extraterrestrial bodies. The same nanofabrication techniques that are used to produce a microfluidics device are also capable of synthesizing extremely high-surface-area templates in precise locations, and coating those surfaces with conformal films to manipulate their surface properties. This methodology has been successfully applied at JPL to produce patterned and coated silicon nanotips (also known as black silicon) to manipulate the hydrophilicity of surfaces to direct the spreading of fluids in microdevices. JPL's ALD technique is an ideal method to produce the highly conformal coatings required for this type of application. Certain materials, such as TiO2, have germicidal and anti-fouling properties when they are illuminated with UV light. The proposed delivery device contacts medicine with this high-surface-area black silicon surface coated with a thin-film germicidal deposited conformally with ALD. The coating can also be illuminated with ultraviolet light for the purpose of sterilization or identification of the medicine itself. This constrained volume that is located immediately prior to delivery into a patient, ensures that the medicine delivery device is inherently sterile. An additional benefit to integrating a high-surface-area template within the fluid channel of a medicine delivery device is that one can envision a number of different functional coatings that could facilitate the capture and analysis of either microbial contaminants or the medicine itself. For example, one could attach antibodies or some other binding agent with a specific affinity to the silicon nanotip template. Once a target molecule or microbe is bound to the high-surface- area template, one could use an optical analytical technique such as fluorescence or adsorption to determine the identity and potentially the concentration of the species of interest. By illuminating the bound species from the back, it may also be possible to probe only the molecules with an evanescent wave, making detection of the species from the front side of the device much simpler.

Shearn, Michael J.↗
DOE OSTI2023

Do parcel lockers reduce delivery times? Evidence from the field

Common-carrier parcel lockers have emerged as a secure, automated, self-service means of delivery consolidation in congested urban areas, which are believed to mitigate last-mile delivery challenges through reducing out-of-vehicle delivery times and consequently vehicle dwell times at the curb. However, little research exists to empirically demonstrate the environmental and efficiency gains from this technology. In this study, we designed a nonequivalent groups pre-test/post-test control experiment to estimate the causal effects of a parcel locker on delivery times in a residential building in downtown Seattle, WA. Here, the causal effects are measured in terms of vehicle dwell time and the time delivery couriers spend inside the building, through the difference-in-difference method and using a similar nearby residential building as a control. The results showed a statistically significant decrease in time spent inside the building, and small yet insignificant reduction in delivery vehicle dwell time at the curb. The locker was also well received by the building managers and residents.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2021

Nanoparticle cellular internalization is not required for RNA delivery to mature plant leaves

Rapidly growing interest in the nanoparticle-mediated delivery of DNA and RNA to plants requires a better understanding of how nanoparticles and their cargoes translocate in plant tissues and into plant cells. However, little is known about how the size and shape of nanoparticles influence transport in plants and the delivery efficiency of their cargoes, limiting the development of nanotechnology in plant systems. In this study we employed non-biolistically delivered DNA-modified gold nanoparticles (AuNPs) of various sizes (5-20 nm) and shapes (spheres and rods) to systematically investigate their transport following infiltration into Nicotiana benthamiana leaves. Generally, smaller AuNPs demonstrated more rapid, higher and longer-lasting levels of association with plant cell walls compared with larger AuNPs. We observed internalization of rod-shaped but not spherical AuNPs into plant cells, yet, surprisingly, 10 nm spherical AuNPs functionalized with small-interfering RNA (siRNA) were the most efficient at siRNA delivery and inducing gene silencing in mature plant leaves. These results indicate the importance of nanoparticle size in efficient biomolecule delivery and, counterintuitively, demonstrate that efficient cargo delivery is possible and potentially optimal in the absence of nanoparticle cellular internalization. Additionally, our results highlight nanoparticle features of importance for transport within plant tissues, providing a mechanistic overview of how nanoparticles can be designed to achieve efficacious biocargo delivery for future developments in plant nanobiotechnology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Partner with a Third-Party Delivery Service or Not? A Prediction-and-Decision Tool for Restaurants Facing Takeout Demand Surges During a Pandemic

Amidst the COVID-19 pandemic, restaurants become more reliant on no-contact pick-up or delivery ways for serving customers. As a result, they need to make tactical planning decisions such as whether to partner with online platforms, to form their own delivery team, or both. In this paper, we develop an integrated prediction-decision model to analyze the profit of combining the two approaches and to decide the needed number of drivers under stochastic demand. We first use the susceptible-infected-recovered (SIR) model to forecast future infected cases in a given region and then construct an autoregressive-moving-average (ARMA) regression model to predict food-ordering demand. Using predicted demand samples, we formulate a stochastic integer program to optimize food delivery plans. We conduct numerical studies using COVID-19 data and food-ordering demand data collected from local restaurants in Nuevo Leon, Mexico, from April to October 2020, to show results for helping restaurants build contingency plans under rapid market changes. Our method can be used under unexpected demand surges, various infection/vaccination status, and demand patterns. Here, our results show that a restaurant can benefit from partnering with third-party delivery platforms when (i) the subscription fee is low, (ii) customers can flexibly decide whether to order from platforms or from restaurants directly, (iii) customers require more efficient delivery, (iv) average delivery distance is long, or (v) demand variance is high.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2024

Delivering Clean Air in Denver: Propane Trucks and Infrastructure in Mail Delivery Application

In 2021, Drive Clean Colorado, a Denver-based Clean Cities coalition, initiated the deployment of five Class 6 medium-duty propane autogas delivery trucks into a United States Postal Service (USPS) mail delivery contractor fleet with the goal of providing a proof-of-concept demonstration for mail delivery fleets nationwide. Funded by the U.S. Department of Energy's Office of Energy Efficiency & Renewable Energy, the project, titled "Delivering Clean Air in Denver: Propane Trucks and Infrastructure in Mail Delivery Application," enabled the purchase and deployment of the propane-powered trucks, refueling infrastructure, and supporting analysis by the National Renewable Energy Laboratory (NREL). Key objectives of the analysis included calculating the propane vehicles' emissions reductions, analyzing the costs and operational performance of the propane fleet compared to conventional diesel-powered vehicles, and evaluating the viability of propane as a clean and cost-effective alternative to conventional diesel trucks (AFDC 2023b, 2023c). The primary goal of the project was to demonstrate alternative fuel vehicles in a mail transport application and evaluate the viability of propane as a clean and cost-effective alternative to conventional diesel trucks. This proof-of-concept demonstration is expected to lead to improved understanding of the performance attributes, costs, and operational issues to inform technology adoption decisions, helping to spur market transformation toward lower-emission truck fleets. By reducing the risk of first adoption, potential exists to transform the U.S. Postal Service (USPS) mail delivery system into a lower-carbon national fleet. This technical report details the vehicle duty cycle characterization and fleet cost and performance comparison performed by the National Renewable Energy Laboratory, in addition to estimated emissions reductions for delivery operations.

33 ADVANCED PROPULSION SYSTEMS↗
NASA NTRS1996

Transmembrane transport of peptide type compounds: prospects for oral delivery

Synthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.

NASA Discipline Regulatory Physiology↗
DOE OSTI2018

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014–2015

Highlights: • Lack of data on maternal exposure to toxic and trace elements in Africa. • Longitudinal blood measurements of Pb, Cd, Zn, Cu and Mn during pregnancy in Benin. • Evidence of maternal exposure to Pb and Cd. • Identification of potential sources for Pb exposure during pregnancy. During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24–0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5–52.0), with 31.3% of blood Pb levels above the 50 μg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 μg/L (4894–5822), 1609 μg/L (1295–1771) and 16.0 μg/L (12.5–20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Efficacy and Delivery of Novel FAST Agents for Coronaviruses

We proposed to test and develop advanced delivery for novel agents from our collaborators Facile Accelerated Specific Therapeutics (FAST) platform to reduce coronavirus replication. Sachi Bioworks Inc., Prof. Anushree Chatterjee, and Prof. Prashant Nagpal at the University of Colorado Boulder have developed a bioinformatics and synthesis pipeline to produce sequence specific theranostic agents (agents that can be therapies and/or diagnostics) that are inherently transported into the cytoplasm of mammalian host cells and sequence-specifically interfere in nucleic acid replication. The agent comprises a small nanoparticle (2-5 nm) chosen for ideal cellular transport and/or imaging conjugated to a short, synthetic DNA analog oligomer designed for binding to one or more target viral sequences. The sequence specific binding of the FAST agent to its target prevents nucleic acid replication due to its high affinity binding. While the small nanoparticle facilitates delivery in vitro, we plan to package the FAST agents into a larger nanoparticle (80-300 nm) for future in vivo delivery applications. Our team at Sandia has expertise encapsulating biomolecules including protein, DNA, and RNA into solid lipid nanoparticles (LNP) and lipid coated mesoporous silica nanoparticles (LC-MSN) and shown successful delivery in mouse models to multiple tissues. Our team focused on formulation parameters for FAST agents into lipid nanoparticles (LNP) and lipid coated mesoporous silica nanoparticles (LC-MSN) for enhanced delivery and/or efficacy and in vivo translation. We used lipid formulas that have been shown in literature to facility in vitro and more importantly, in vivo delivery. In our work discussed below, we successfully demonstrate loading and release of FAST agents on silica core and stable LC-MSN in a reasonable size range for in vivo testing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Review of Amendment Delivery and Distribution Methods, and Relevance to Potential In Situ Source Area Treatment at the Hanford Site

The U.S. Department of Energy’s Hanford Site in southeastern Washington State is a complex of multiple facilities where historical release events in the Central Plateau area have resulted in subsurface contamination of the vadose zone, a perched-water zone, and underlying aquifer. Although some contaminants have already migrated through the vadose zone into the groundwater, contaminants remaining in the unsaturated zone are a potential long-term risk as a source for further groundwater contamination. Moreover, a perched-water zone located in the 200-DV-1 Operable Unit at Hanford creates further remediation difficulties. Remediation options are limited for contaminants located in the vadose and perched-water zones within the Central Plateau due to considerable depth, co-located contaminants, and complexities associated with physical and biogeochemical heterogeneities. Existing comprehensive reviews discuss potential remedial technologies relevant to Hanford Site conditions (e.g., deep vadose zone and perched water) and provide treatment technology recommendations. Many of the recommended in situ remediation technologies rely on introduction of amendments into the subsurface to achieve remedial goals. However, there are currently few review or guidance documents that provide a comprehensive look at mechanisms and considerations related to amendment delivery and distribution. This document summarizes amendment types, delivery techniques, subsurface access methods, and the applicability of delivery methods and amendments for specific subsurface target zones, including in the context of Hanford Central Plateau applications. Guidance on the appropriateness of a remedial technology for a specific site and contaminant is not included within this document. Rather, this document is intended to be used when considering remediation technologies and the associated amendments. An overview of amendment types (i.e., liquid, gas, and solids) and access/distribution methods used in subsurface remediation is provided, along with discussion of the maturity level (low, medium, or high), advantages, and limitations that relate to the potential effectiveness of each approach in the context of site-specific factors (subsurface geology, geochemistry, contaminant properties, etc.). There are many Hanford Site-specific factors that influence the suitability and appropriateness of amendment delivery strategies. Excluding amendment delivery approaches that are unsuitable for the Hanford context, each approach was assessed for applicability to the following target zones: unsaturated high permeability, unsaturated low permeability, perched water, saturated high permeability, and saturated low permeability zones. This compilation and discussion related to amendment delivery mechanisms provides a useful resource for evaluating remedial alternatives for source area contamination in the Hanford Central Plateau.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS2000

Deep Space Systems Technology Program Future Deliveries

NASA is in a period of frequent launches of low cost deep space missions with challenging performance needs. The modest budgets of these missions make it impossible for each to develop its own technology, therefore, efficient and effective development and insertion of technology for these missions must be approached at a higher level than has been done in the past. The Deep Space Systems Technology Program (DSST), often referred to as X2000, has been formed to address this need. The program is divided into a series of "Deliveries" that develop and demonstrate a set of spacecraft system capabilities with broad applicability for use by multiple missions. The First Delivery Project, to be completed in 2001, will provide a one MRAD-tolerant flight computer, power switching electronics, efficient radioisotope power source, and a transponder with services at 8.4 GHz and 32 GHz bands. Plans call for a Second Delivery in late 2003 to enable complete deep space systems in the 10 to 50 kg class, and a Third Delivery built around Systems on a Chip (extreme levels of electronic and microsystems integration) around 2006. Formulation of Future Deliveries (past the First Delivery) is ongoing and includes plans for such developments as highly miniaturized digital/analog/power electronics, optical communications, multifunctional structures, miniature lightweight propulsion, advanced thermal control techniques, highly efficient radioisotope power sources, and a unified flight ground software architecture to support the needs of future highly intelligent space systems. All developments are targeted at broad applicability and reuse, and will be commercialized within the US.

Salvo, Christopher G.↗
NASA NTRS2016

Assessment of Delivery Accuracy in an Operational-Like Environment

In order to enable arrival management concepts and solutions in a Next Generation Air Transportation System (NextGen) environment, ground-based sequencing and scheduling functions were developed to support metering operations in the National Airspace System. These sequencing and scheduling tools are designed to assist air traffic controllers in developing an overall arrival strategy, from enroute down to the terminal area boundary. NASA developed a ground system concept and protoype capability called Terminal Sequencing and Spacing (TSAS) to extend metering operations into the terminal area to the runway. To demonstrate the use of these scheduling and spacing tools in an operational-like environment, the FAA, NASA, and MITRE conducted an Operational Integration Assessment (OIA) of a prototype TSAS system at the FAA's William J. Hughes Technical Center (WJHTC). This paper presents an analysis of the arrival management strategies utilized and delivery accuracy achieved during the OIA. The analysis demonstrates how en route preconditioning, in various forms, and schedule disruptions impact delivery accuracy. As the simulation spanned both enroute and terminal airspace, the use of Ground Interval Management - Spacing (GIM-S) enroute speed advisories was investigated. Delivery accuracy was measured as the difference between the Scheduled Time of Arrival (STA) and the Actual Time of Arrival (ATA). The delivery accuracy was computed across all runs conducted during the OIA, which included deviations from nominal operations which are known to commonly occur in real operations, such as schedule changes and missed approaches. Overall, 83% of all flights were delivered into the terminal airspace within +/- 30 seconds of their STA and 94% of flights were delivered within +/- 60 seconds. The meter fix delivery accuracy standard deviation was found to be between 36 and 55 seconds across all arrival procedures. The data also showed when schedule disruptions were excluded, the percentage of aircraft delivered within +/- 30 seconds was between 85 and 90% across the various arrival procedures at the meter fix. This paper illustrates the ability to meet new delivery accuracy requirements in an operational-like environment using operational systems and NATCA controller participants, while also including common events that might cause disruptions to the schedule and overall system.

Air Traffic Scheduling↗
NASA NTRS2018

Angled Radial Fuel/Air Delivery System for Combustor

A combustor is provided. The combustor may comprise an axial fuel delivery system, and a radial fuel delivery system aft of the axial fuel delivery system. The radial fuel delivery system may be configured to direct fuel at least partially towards the axial fuel delivery system. A radial fuel delivery system is also provided. The system may comprise a combustor including a combustor liner, a mixer coupled to the combustor liner, and a nozzle disposed within the mixer, wherein the mixer and the nozzle are configured to direct fuel in a direction at least partially forward.

Kim, Wookyung↗
DOE OSTI2020

Designing a drone delivery network with automated battery swapping machines

Drones are projected to alter last-mile delivery, but their short travel range is a concern. In this study, we propose a drone delivery network design using automated battery swapping machines (ABSMs) to extend ranges. The design minimizes the long-term delivery costs, including ABSM investment, drone ownership, and cost of the delivery time, and locates ABSMs to serve a set of customers. We build a mixed-integer nonlinear program that captures the nonlinear waiting time of drones at ABSMs. To solve the problem, we create an exact solution algorithm that finds the globally optimal solution using a derivative-supported cutting-plane method. To validate the applicability of our program, we conduct a case study on the Chicago Metropolitan area using cost data from leading ABSM manufacturer and geographical data from the planning and operations language for agent-based regional integrated simulation (more commonly known as POLARIS). A sensitivity analysis identifies that ABSM service times and costs are the key parameters impacting the long-term adoption of drone delivery.

25 ENERGY STORAGE↗
DOE OSTI2022

Poly( N -vinylpyrrolidone)- block -Poly(dimethylsiloxane)- block -Poly( N -vinylpyrrolidone) Triblock Copolymer Polymersomes for Delivery of PARP1 siRNA to Breast Cancers

Nearly 20% of HER2-positive breast cancers develop resistance to HER2-targeted therapies requiring the use of advanced therapies. Silencing RNA therapy may be a powerful modality for treating resistant HER2 cancers due to its high specificity and low toxicity. However, the systemic administration of siRNAs requires a safe and efficient delivery platform because of siRNA’s low stability in physiological fluids, inefficient cellular uptake, immunoreactivity, and rapid clearance. We have developed theranostic polymeric vesicles to overcome these hurdles for encapsulation and delivery of small functional molecules and PARP1 siRNA for in vivo delivery to breast cancer tumors. The 100 nm polymer vesicles were assembled from biodegradable and non-ionic poly(N-vinylpyrrolidone) 14 -block-poly(dimethylsiloxane) 47 -block-poly(N-vinylpyrrolidone) 14 triblock copolymer PVPON 14 -PDMS 47 -PVPON 14 using nanoprecipitation and thin-film hydration. We demonstrated that the vesicles assembled from the copolymer covalently tagged with the Cy5.5 fluorescent dye for in vivo imaging could also encapsulate the model drug with high loading efficiency (40%). The dye-loaded vesicles were accumulated in tumors after 18 h circulation in 4TR breast tumor-bearing mice via passive targeting. We found that PARP1 siRNA encapsulated into the vesicles was released intact (13%) into solution by the therapeutic ultrasound treatment as quantified by gel electrophoresis. Additionally, the PARP1 siRNA-loaded polymersomes inhibited the proliferation of MDA-MB-361TR cells by 34% after 6 days of treatment by suppressing the NF-kB signaling pathway, unlike their scrambled siRNA-loaded counterparts. Finally, the treatment by PARP1 siRNA-loaded vesicles prolonged the survival of the mice bearing 4T1 breast cancer xenografts, with the 4-fold survival increase, unlike the untreated mice after 3 weeks following the treatment. These biodegradable, non-ionic PVPON 14 -PDMS 47 -PVPON 14 polymeric nanovesicles capable of the efficient encapsulation and delivery of PARP1 siRNA to successfully knock down PARP1 in vivo can provide an advanced platform for the development of precision-targeted therapeutic carriers, which could help develop highly effective drug delivery nanovehicles for breast cancer gene therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

In Situ Loading and Delivery of Short Single- and Double-Stranded DNA by Supramolecular Organic Frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double end-labeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF–nucleic acid ratios. In addition to high delivery efficiencies, the water-soluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2017

A Multi-Modality Mobility Concept for a Small Package Delivery UAV

This paper will discuss a different approach to the typical notional small package delivery drone concept. Most delivery drone concepts employ a point-to-point aerial delivery CONOPS (Concept of Operations) from a warehouse directly to the front or back yards of a customers residence or a commercial office space. Instead, the proposed approach is somewhat analogous to current postal deliveries: a small aerial vehicle flies from a warehouse to designated neighborhood VTOL (Vertical Take-Off and Landing) landing spots where the aerial vehicle then converts to a "roadable" (ground-mobility) vehicle that then transits on sidewalks and/or bicycle paths till it arrives to the residence/office drop-off points. This concept and associated platform or vehicle will be referred in this paper as MICHAEL (Multimodal Intra-City Hauling and Aerial-Effected Logistics) concept. It is suggested that the MICHAEL concept potentially results in a more community friendly "delivery drone" approach.

UAV↗
DOE OSTI2024

Targeted nonviral delivery of genome editors in vivo

Cell-type-specific in vivo delivery of genome editing molecules is the next breakthrough that will drive biological discovery and transform the field of cell and gene therapy. Here, we discuss recent advances in the delivery of CRISPR-Cas genome editors either as preassembled ribonucleoproteins or encoded in mRNA. Both strategies avoid pitfalls of viral vector-mediated delivery and offer advantages including transient editor lifetime and potentially streamlined manufacturing capability that are already proving valuable for clinical use. We review current applications and future opportunities of these emerging delivery approaches that could make genome editing more efficacious and accessible in the future.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and, consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. - Highlights: • A carborane-bearing pullulan nanogel is developed as a boron delivery agent. • The nanogels are cell-friendly and show effective cell uptake for drug delivery. • The nanogels show passive tumor targeting by enhanced permeation and retention.

60 APPLIED LIFE SCIENCES↗