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At least 91 records · Page 5

Early Systems Integration Strengthens Orion Medical Capabilities

The Orion spacecraft has significant mass and volume constraints, which limits resources that can be provided for medical use. Sharing of resources between vehicle systems is therefore required to meet design requirements. This presentation will illustrate resource sharing within the Orion vehicle using oxygen as a case study.

C Haas↗

Advancements in medicine from aerospace research.

Discussion of a NASA-sponsored medical program under which work is done by multidiscipline teams to provide an interface between aerospace and medicine. A prosthetic urethral valve, an ear oximeter for measurement of oxygen content in the blood, a radiation dosimeter and an electromyographic muscle trainer are noted as the products of this program.

Wooten, F. T.↗

Medical Lessons Learned from the Exploration Atmospheres Study

Background: The National Aeronautics and Space Administration’s (NASA) Exploration Atmospheres study (EA) was done to evaluate alternative cabin atmospheres for future spacecraft designs and planetary surface exploration of the Moon, Mars and beyond. Deep space exploration involves creating habitats and environments safe for human occupancy and means to explore the outside environment (extravehicular activities, EVA). In order to validate alternative atmospheres and pre-spacewalk procedures, the EA study was conducted to evaluate factors such as hypoxia risks, denitrogenation protocols, food limitations, medications, and the impact of other factors on human performance. Overview: Space travel is constrained by mass, volume, power and the cost of vehicle development, which creates tradeoffs in various capabilities, including breathing gasses. Higher atmospheric pressure in a vehicle means more gas, and a stronger containment vessel/habitat; while lower pressure requires higher oxygen partial pressure, which may increase fire risk. NASA’s EA study evaluated a proposed alternative cabin environment (8.2 psia, 34% Oxygen), for future spacecraft habitat, and planetary EVAs. EA included both a 3-day and a 11-day trial. These trials included a depressurization and saturation to 8.2psi at 34% O2 with additional depresses to 4.3 psia at 85% O2 for simulated EVAs, (1 EVA during the 3-day and 5 during the 11-day trials). Discussion: Planning for and executing the medical monitoring and response plan for a trial of this scope was a huge undertaking with no prior practice to fall back on. Food obstacles, sleeping issues, medications, joint injury, equipment limitations, medical privacy, multiple cases of decompression sickness, and even a COVID outbreak among the support team proved challenging. Conclusion: Testing of this nature is an essential part NASA’s preparation for the upcoming Lunar Artemis missions. As spaceflight transitions beyond low earth orbit, to planetary, even more trials of this nature will be required to learn what are the optimal atmospheric and associated operational constraints to maintain the optimal health of the crew and achieve mission objectives.

R Sanders↗

Laser Spectroscopy Multi-Gas Monitor: Results of Technology Demonstration on ISS

Tunable diode laser spectroscopy (TDLS) is an up and coming trace and major gas monitoring technology with unmatched selectivity, range and stability. The technology demonstration of the 4 gas Multi-Gas Monitor (MGM), reported at the 2014 ICES conference, operated continuously on the International Space Station (ISS) for nearly a year. The MGM is designed to measure oxygen, carbon dioxide, ammonia and water vapor in ambient cabin air in a low power, relatively compact device. While on board, the MGM experienced a number of challenges, unplanned and planned, including a test of the ammonia channel using a commercial medical ammonia inhalant. Data from the unit was downlinked once per week and compared with other analytical resources on board, notably the Major Constituent Analyzer (MCA), a magnetic sector mass spectrometer. MGM spent the majority of the time installed in the Nanoracks Frame 2 payload facility in front breathing mode (sampling the ambient environment of the Japanese Experiment Module), but was also used to analyze recirculated rack air. The capability of the MGM to be operated in portable mode (via internal rechargeable lithium ion polymer batteries or by plugging into any Express Rack 28VDC connector) was a part of the usability demonstration. Results to date show unprecedented stability and accuracy of the MGM vs. the MCA for oxygen and carbon dioxide. The ammonia challenge (approx. 75 ppm) was successful as well, showing very rapid response time in both directions. Work on an expansion of capability in a next generation MGM has just begun. Combustion products and hydrazine are being added to the measurable target analytes. An 8 to 10 gas monitor (aka Gas Tricorder 1.0) is envisioned for use on ISS, Orion and Exploration missions.

Mudgett, Paul D.↗

To develop a spectral analyzer for physiological and medical use

Scientific requirements necessary to develop a spectral analyzer for monitoring mammalian subjects, are discussed. The analyzer measures dynamic or time dependent data as a measure of the subjects operating status. Measurable data include metabolic rate, body temperature, and blood constituents like glucose, oxygen, and carbon dioxide, and lactic acid. Metabolic cycles were found with periodicities in the range of minutes and hours; longer cycles in body weight (3 1/2 days and 60 days), indicative of metabolic processes, were also found.

Iberall, A.↗

Conducting Closed Habitation Experiments: Experience from the Lunar Mars Life Support Test Project

The Lunar-Mars Life Support Test Project (LMLSTP) was conducted from 1995 through 1997 at the National Aeronautics and Space Administration s (NASA) Johnson Space Center (JSC) to demonstrate increasingly longer duration operation of integrated, closed-loop life support systems that employed biological and physicochemical techniques for water recycling, waste processing, air revitalization, thermal control, and food production. An analog environment for long-duration human space travel, the conditions of isolation and confinement also enabled studies of human factors, medical sciences (both physiology and psychology) and crew training. Four tests were conducted, Phases I, II, IIa and III, with durations of 15, 30, 60 and 91 days, respectively. The first phase focused on biological air regeneration, using wheat to generate enough oxygen for one experimental subject. The systems demonstrated in the later phases were increasingly complex and interdependent, and provided life support for four crew members. The tests were conducted using two human-rated, atmospherically-closed test chambers, the Variable Pressure Growth Chamber (VPGC) and the Integrated Life Support Systems Test Facility (ILSSTF). Systems included test articles (the life support hardware under evaluation), human accommodations (living quarters, kitchen, exercise equipment, etc.) and facility systems (emergency matrix system, power, cooling, etc.). The test team was managed by a lead engineer and a test director, and included test article engineers responsible for specific systems, subsystems or test articles, test conductors, facility engineers, chamber operators and engineering technicians, medical and safety officers, and science experimenters. A crew selection committee, comprised of psychologists, engineers and managers involved in the test, evaluated male and female volunteers who applied to be test subjects. Selection was based on the skills mix anticipated for each particular test, and utilized information from psychological and medical testing, data on the knowledge, experience and skills of the applicants, and team building exercises. The design, development, buildup and operation of test hardware and documentation followed the established NASA processes and requirements for test buildup and operation.

Barta, Daniel J.↗

Conducting Closed Habitation Experiments: Experience from the Lunar Mars Life Support Test Project

The Lunar-Mars Life Support Test Project (LMLSTP) was conducted from 1995 through 1997 at the National Aeronautics and Space Administration s (NASA) Johnson Space Center (JSC) to demonstrate increasingly longer duration operation of integrated, closed-loop life support systems that employed biological and physicochemical techniques for water recycling, waste processing, air revitalization, thermal control, and food production. An analog environment for long-duration human space travel, the conditions of isolation and confinement also enabled studies of human factors, medical sciences (both physiology and psychology) and crew training. Four tests were conducted, Phases I, II, IIa and III, with durations of 15, 30,60 and 91 days, respectively. The first phase focused on biological air regeneration, using wheat to generate enough oxygen for one experimental subject. The systems demonstrated in the later phases were increasingly complex and interdependent, and provided life support for four crew members. The tests were conducted using two human-rated, atmospherically-closed test chambers, the Variable Pressure Growth Chamber (VPGC) and the Integrated Life Support Systems Test Facility (ILSSTF). Systems included test articles (the life support hardware under evaluation), human accommodations (living quarters, kitchen, exercise equipment, etc.) and facility systems (emergency matrix system, power, cooling, etc.). The test team was managed by a lead engineer and a test director, and included test article engineers responsible for specific systems, subsystems or test articles, test conductors, facility engineers, chamber operators and engineering technicians, medical and safety officers, and science experimenters. A crew selection committee, comprised of psychologists, engineers and managers involved in the test, evaluated male and female volunteers who applied to be test subjects. Selection was based on the skills mix anticipated for each particular test, and utilized information from psychological and medical testing, data on the knowledge, experience and skills of the applicants, and team building exercises. The design, development, buildup and operation of test hardware and documentation followed the established NASA processes and requirements for test buildup and operation.

Barta, Daniel J.↗

Launch-Off-Need Shuttle Hubble Rescue Mission: Medical Issues

The Space Shuttle Hubble repair mission (STS-125) is unique in that a rescue mission (STS-400) has to be ready to launch before STS-125 life support runs out should the vehicle become stranded. The shuttle uses electrical power derived from fuel cells that use cryogenic oxygen and hydrogen (CRYO) to run all subsystems including the Environmental Control System. If the STS-125 crew cannot return to Earth due to failure of a critical subsystem, they must power down all nonessential systems and wait to be rescued by STS-400. This power down will cause the cabin temperature to be 60 F or less and freeze the rest of the vehicle, preventing it from attempting a reentry. After an emergency has been declared, STS-125 must wait at least 7 days to power down since that is the earliest that STS-400 can be launched. Problem The delayed power down of STS-125 causes CYRO to be consumed at high rates and limits the survival time after STS-400 launches to 10 days or less. CRYO will run out sooner every day that the STS-400 launch is delayed (weather at launch, technical issues etc.). To preserve CRYO and lithium hydroxide (LiOH - carbon dioxide removal) the crew will perform no exercise to reduce their metabolic rates, yet each deconditioned STS-125 crewmember must perform an EVA to rescue himself. The cabin may be cold for 10 days, which may cause shivering, increasing the metabolic rate of the STS-125 crew. Solution To preserve LiOH, the STS-125 manifest includes nutrition bars with low carbohydrate content to maintain crew respiratory quotient (RQ) below 0.85 as opposed to the usual shuttle galley food which is rich in carbohydrates and keeps the RQ at approximately 0.95. To keep the crew more comfortable in the cold vehicle warm clothing also has been included. However, with no exercise and limited diet, the deconditioned STS-125 crew returning on STS-400 may not be able to egress the vehicle autonomously requiring a supplemented crash-and-rescue capability.

Hamilton, Douglas↗

Aging Mechanisms of Broad Area High-Power ~800nm Laser Diodes

Improved lifetime of high-power broad area laser diodes will enhance their utility for manufacturing, scientific, and medical laser systems. However, factors contributing to gradual degradation of diode laser performance are not fully understood. Here we study the aging mechanisms of ~800 nm aluminum-free laser diodes grown by solid-source MBE. Oxygen was intentionally introduced at three different concentration levels into the quantum well (QW) and waveguide (WG) at concentrations <5×10 15 cm -3 . Diode power, slope efficiency (SE th ), threshold current (I th ), and device parameters such as QW and WG lifetimes were measured at discrete time steps throughout the aging run. The data show that lasing characteristics prior to aging are degraded by oxygen introduction, but the gradual power degradation rate of ~5% over 500 hours at current density 1.74 kA/cm 2 does not change with oxygen concentration. Aging-induced changes in nonradiative lifetimes and threshold were observed for shorter aging times, but stabilized after ~100 hrs. and cannot explain the observed power degradation. This suggests that gradual degradation in these devices is not due to nonradiative recombination at low levels of point defects. The data shows that this degradation results primarily from changes in slope efficiency, and simulation of these results suggests that the power degradation arises from increased intracavity absorption (ICA). Efforts to slow ICA growth, instead of efforts to control low levels of nonradiative recombination centers, may be the most fruitful path forward to improve laser diode lifetime.

42 ENGINEERING↗

Enhanced Light Outcoupling from OLEDs Fabricated on Novel Low-Cost Patterned Plastic Substrates of Varying Periodicity

OLEDs continue to make strides in display applications, but their commercial utilization in solid-state lighting (SSL) is lagging. An ongoing challenge, in particular for manufacturing, is the need for enhanced efficiency and hence the necessity to increase in an inexpensive approach the extraction of the light generated inside the OLED into the forward (viewing) hemisphere. In conventional OLEDs fabricated on a transparent flat anode coated on glass, the external quantum efficiency (EQE) is only ~20%. About 50% of the light is lost to internal waveguiding in the high refractive index (RI) organic + ITO anode layers and to surface plasmon polaritons (SPPs) at the organic/metal cathode interface. Another ~30% of the light is externally waveguided in the substrate to its edges. While extraction of the externally waveguided light is commonly addressed by adding a microlens array (MLA) or a scattering layer at the substrate’s air-side, light outcoupling increases by only ~1.6-1.7x (vs up to 2.5x in improving from ~20% to ~50%). The use of a hemispherical lens or an index matching fluid (IMF) at the substrate/photodetector (PD) interface increases the outcoupling by at least 2x; these approaches however, are not viable industrially, and even a MLA is sometimes undesirable due to its non-planar, scattering structure. In multi-stack tandem OLEDs, where the metal cathode is far from the emitting zone(s), the impact of photons loss to SPPs decreases. Our project addressed the ~50% loss to the internally waveguided light and SPPs. We evaluated OLEDs fabricated on patterned or planarized plastic substrates manufactured in a cost-effective approach compatible with a roll-to-roll (R2R) process. The OLEDs were either (i) patterned to various degrees depending on the pitch a and height or depth h of the pattern features or (ii) planar, with a pattern buried under a flat high RI planarization layer. We demonstrated that the outcoupling from green patterned OLEDs reaches ~50% by mitigating plasmon–related loss and internal waveguiding, even without the addition of a MLA, a hemispherical lens, or IMF. Simulations conducted in parallel with the experimental effort demonstrated how diffraction by conformally corrugated OLEDs increases the outcoupling to >60%. Structures with varying pitch values were also simulated indicating that combining domains of varying pitch could increase outcoupling to 55-60%. Experimentally, we additionally assessed the role a and h in determining not only the OLED efficiencies, but also their structural properties, i.e., the uniformity and conformality throughout the OLED stack. As planar OLEDs are preferred over corrugated devices, we studied different patterns in plastic substrates that were planarized by a high RI formulation. Planar green OLEDs on such structures showed enhanced efficiencies with EQEs larger than 60% with the addition of an IMF (to extract the substrate mode) at the substrate/Si PD interface. White OLEDs showed EQEs of 45.5%. Plastic substrates are currently less attractive than glass substrates due to drawbacks such as permeability to water vapor and oxygen, and in some cases thermal instability. Plastic substrates however, are flexible and easy to handle unlike thin flexible glass, and once transparent thin barrier films are available, they will become more attractive; they are already of interest in medical applications. Importantly, as it is easy to generate various patterns in different plastic materials, they provide excellent means for assessing and optimizing enhancing extracting structures. Such structures can also be transferred to glass substrates with some process modifications. The technical effectiveness and economic feasibility of the project lie in the patterning of the extracting plastic substrates in an approach that is scalable to R2R manufacturing. R2R processes are of drastically lower-cost than batch or single-unit fabrication. The patterned plastic can be a part of an integrated substrate either plastic or glass, which includes also a MLA or a planar layer with embedded scattering particles, as well as a conductive metal mesh/electrode design. SSL is environmentally-friendly and as OLED SSL becomes more efficient it will reduce electricity consumption, and hence lighting cost, as well as produce less expensive attractive lighting fixtures. Our university-industry collaboration is hence of major benefit to the public as it demonstrates the feasibility of manufacturing optimized extracting substrates for highly efficient OLEDs for SSL in a future R2R process, which would drastically reduce the manufacturing cost and increase production in the USA. Moreover, newly developed methods by our team allow low-cost roll manufactured substrates to be transferred to flexible or rigid glass substrates, which solves the plastic substrate barrier issues, and when combined with device encapsulation will increase the OLEDs’ environmental stability.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

An Evidence-based Approach to Developing a Management Strategy for Medical Contingencies on the Lunar Surface: The NASA/Haughton-Mars Project (HMP) 2006 Lunar Medical Contingency Simulation at Devon Island

The lunar architecture for future sortie and outpost missions will require humans to serve on the lunar surface considerably longer than the Apollo moon missions. Although the Apollo crewmembers sustained few injuries during their brief lunar surface activity, injuries did occur and are a concern for the longer lunar stays. Interestingly, lunar medical contingency plans were not developed during Apollo. In order to develop an evidence-base for handling a medical contingency on the lunar surface, a simulation using the moon-Mars analog environment at Devon Island, Nunavut, high Canadian Arctic was conducted. Objectives of this study included developing an effective management strategy for dealing with an incapacitated crewmember on the lunar surface, establishing audio/visual and biomedical data connectivity to multiple centers, testing rescue/extraction hardware and procedures, and evaluating in suit increased oxygen consumption. Methods: A review of the Apollo lunar surface activities and personal communications with Apollo lunar crewmembers provided the knowledge base of plausible scenarios that could potentially injure an astronaut during a lunar extravehicular activity (EVA). Objectives were established to demonstrate stabilization and transfer of an injured crewmember and communication with ground controllers at multiple mission control centers. Results: The project objectives were successfully achieved during the simulation. Among these objectives were extraction from a sloped terrain by a two-member crew in a 1 g analog environment, establishing real-time communication to multiple centers, providing biomedical data to flight controllers and crewmembers, and establishing a medical diagnosis and treatment plan from a remote site. Discussion: The simulation provided evidence for the types of equipment and methods for performing extraction of an injured crewmember from a sloped terrain. Additionally, the necessary communications infrastructure to connect multiple centers worldwide was established from a remote site. The surface crewmembers were confronted with a number of unexpected scenarios including environmental, communications, EVA suit, and navigation challenges during the course of the simulation which provided insight into the challenges of carrying out a medical contingency in an austere environment. The knowledge gained from completing the objectives will be incorporated into the exploration medical requirements involving an incapacitated astronaut on the lunar surface.

Scheuring, R. A.↗

A 99 percent purity molecular sieve oxygen generator

Molecular sieve oxygen generating systems (MSOGS) have become the accepted method for the production of breathable oxygen on military aircraft. These systems separate oxygen for aircraft engine bleed air by application of pressure swing adsorption (PSA) technology. Oxygen is concentrated by preferential adsorption in nitrogen in a zeolite molecular sieve. However, the inability of current zeolite molecular sieves to discriminate between oxygen and argon results in an oxygen purity limitations of 93-95 percent (both oxygen and argon concentrate). The goal was to develop a new PSA process capable of exceeding the present oxygen purity limitations. A novel molecular sieve oxygen concentrator was developed which is capable of generating oxygen concentrations of up to 99.7 percent directly from air. The process is comprised of four absorbent beds, two containing a zeolite molecular sieve and two containing a carbon molecular sieve. This new process may find use in aircraft and medical breathing systems, and industrial air separation systems. The commercial potential of the process is currently being evaluated.

Miller, G. W.↗

Medical Gas Analyzer

The Remote Monitoring System (RMS) is manufactured by Perkin Elmer Corporation. The principal component of the RMS was originally developed for spacecraft use to monitor astronaut's respiratory gases in NASA's Gemini and Apollo program. At Wishard Memorial Hospital in Indianapolis, IN, the RMS is used in operating rooms for analysis of anesthetic gases and measurement of oxygen, carbon dioxide and nitrogen concentrations. It assures that the patient undergoing surgery has the proper breathing environment.

Source record↗

Adsorption separation of heavier isotope gases in subnanometer carbon pores

Isotopes of heavier gases including carbon ( 13 C/ 14 C), nitrogen ( 13 N), and oxygen ( 18 O) are highly important because they can be substituted for naturally occurring atoms without significantly perturbing the biochemical properties of the radiolabelled parent molecules. These labelled molecules are employed in clinical radiopharmaceuticals, in studies of brain disease and as imaging probes for advanced medical imaging techniques such as positron-emission tomography (PET). Established distillation-based isotope gas separation methods have a separation factor ( S ) below 1.05 and incur very high operating costs due to high energy consumption and long processing times, highlighting the need for new separation technologies. Here, we show a rapid and highly selective adsorption-based separation of 18 O 2 from 16 O 2 with S above 60 using nanoporous adsorbents operating near the boiling point of methane (112 K), which is accessible through cryogenic liquefied-natural-gas technology. A collective-nuclear-quantum effect difference between the ordered 18 O 2 and 16 O 2 molecular assemblies confined in subnanometer pores can explain the observed equilibrium separation and is applicable to other isotopic gases.

36 MATERIALS SCIENCE↗

"Application of Tunable Diode Laser Spectrometry to Isotopic Studies for Exobiology"

Computer-controlled electrically-activated valves for rapid gas-handling have been incorporated into the Stable Isotope Laser Spectrometer (SILS) which now permits rapid filling and evacuating of the sample and reference gas cells, Experimental protocols have been developed to take advantage of the fast gas handling capabilities of the instrument and to achieve increased accuracy which results from reduced instrumental drift during rapid isotopic ratio measurements. Using these protocols' accuracies of 0.5 del (0.05%) have been achieved in measurements of 13C/12C in carbon dioxide. Using the small stable isotope laser spectrometer developed in a related PIDDP project of the Co-I, protocols for acquisition of rapid sequential calibration spectra were developed which resulted in 0.5 del accuracy also being achieved in this less complex instrument. An initial version of software for automatic characterization of tunable diode lasers has been developed and diodes have been characterized in order to establish their spectral output properties. A new state-of-the-art high operating temperature (200 K) mid infrared diode laser was purchased (through NASA procurement) and characterized. A thermo-electrically cooled mid infrared tunable diode laser system for use with high temperature operation lasers was developed. In addition to isotopic ratio measurements of carbon and oxygen, measurements of a third biologically important element (15N/14N in N2O gas) have been achieved to a preliminary accuracy of about 0.2%. Transfer of the basic SILS technology to the commercial sector is proceeding under an unfunded Space Act Agreement between NASA and SpiraMed, a medical diagnostic instrument company. Two patents have been issued. Foreign patents based on these two US patents have been applied for and are expected to be issued. A preliminary design was developed for a thermo-electrically cooled SILS instruments for application to planetary space flight exploration missions.

Sauke, Todd B.↗

Transparent Metal-Salt-Filled Polymeric Radiation Shields

"COR-RA" (colorless atomic oxygen resistant -- radiation shield) is the name of a transparent polymeric material filled with x-ray-absorbing salts of lead, bismuth, cesium, and thorium. COR-RA is suitable for use in shielding personnel against bremsstrahlung radiation from electron-beam welding and industrial and medical x-ray equipment. In comparison with lead-foil and leaded-glass shields that give equivalent protection against x-rays (see table), COR-RA shields are mechanically more durable. COR-RA absorbs not only x-rays but also neutrons and rays without adverse effects on optical or mechanical performance. The formulation of COR-RA with the most favorable mechanical-durability and optical properties contains 22 weight percent of bismuth to absorb x-rays, plus 45 atomic percent hydrogen for shielding against neutrons.

Edwards, David↗

Genetic and behavioral adaptation of Candida parapsilosis to the microbiome of hospitalized infants revealed by in situ genomics, transcriptomics, and proteomics

Background Candida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades. C. parapsilosis has been primarily studied in pure culture, leaving gaps in understanding of its function in a microbiome context. Results. Here, we compare five unique C. parapsilosis genomes assembled from premature infant fecal samples, three of which are newly reconstructed, and analyze their genome structure, population diversity, and in situ activity relative to reference strains in pure culture. All five genomes contain hotspots of single nucleotide variants, some of which are shared by strains from multiple hospitals. A subset of environmental and hospital-derived genomes share variants within these hotspots suggesting derivation of that region from a common ancestor. Four of the newly reconstructed C. parapsilosis genomes have 4 to 16 copies of the gene RTA3, which encodes a lipid translocase and is implicated in antifungal resistance, potentially indicating adaptation to hospital antifungal use. Time course metatranscriptomics and metaproteomics on fecal samples from a premature infant with a C. parapsilosis blood infection revealed highly variable in situ expression patterns that are distinct from those of similar strains in pure cultures. For example, biofilm formation genes were relatively less expressed in situ, whereas genes linked to oxygen utilization were more highly expressed, indicative of growth in a relatively aerobic environment. In gut microbiome samples, C. parapsilosis co-existed with Enterococcus faecalis that shifted in relative abundance over time, accompanied by changes in bacterial and fungal gene expression and proteome composition. Conclusions The results reveal potentially medically relevant differences in Candida function in gut vs. laboratory environments, and constrain evolutionary processes that could contribute to hospital strain persistence and transfer into premature infant microbiomes.

59 BASIC BIOLOGICAL SCIENCES↗

Impact of Surface Chemistry of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles on Protein Corona Formation and Endothelial Cell Uptake, Toxicity, and Barrier Function

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) have been investigated for biomedical applications, including novel contrast agents, magnetic tracers for tumor imaging, targeted drug delivery vehicles, and magneto-mechanical actuators for hyperthermia and thrombolysis. Despite significant progress, recent clinical reports have raised concerns regarding USPION safety related to endothelial cell dysfunction; however, there is limited information on factors contributing to these clinical responses. The influence of USPION surface chemistry on nanoparticle interactions with proteins may impact endothelial cell function leading to adverse responses. Therefore, the goal of this study was to assess the effects of carboxyl-functionalized USPION (CU) or amine-functionalized USPION (AU) (approximately 30 nm diameter) on biological responses in human coronary artery endothelial cells. Increased protein adsorption was observed for AU compared with CU after exposure to serum proteins. Exposure to CU, but not AU, resulted in a concentration-dependent decrease in cell viability and perinuclear accumulation inside cytoplasmic vesicles. Internalization of CU was correlated with endothelial cell functional changes under non-cytotoxic conditions, as evidenced by a marked decreased expression of endothelial-specific adhesion proteins (eg, vascular endothelial-cadherin and platelet endothelial cell adhesion molecule-1) and increased endothelial permeability. Evaluation of downstream signaling indicated endothelial permeability is associated with actin cytoskeleton remodeling, possibly elicited by intracellular events involving reactive oxygen species, calcium ions, and the nanoparticle cellular uptake pathway. This study demonstrated that USPION surface chemistry significantly impacts protein adsorption and endothelial cell uptake, viability, and barrier function. This information will advance the current toxicological profile of USPION and improve development, safety assessment, and clinical outcomes of USPION-enabled medical products.

Toxicology↗