With a clear understanding of its behaviors in biological environment, the polymer micelle is a promising nanocarrier for chemotherapy.
Ultraviolet (UV) solar radiation is a leading cause of skin disease. Quantitative, continuous knowledge of exposure levels can enhance awareness and lead to improved health outcomes. Devices that offer this type of measurement capability in formats that can seamlessly integrate with the skin are therefore of interest. This paper introduces materials, device designs, and data acquisition methods for a skin‐like, or “epidermal,” system that combines colorimetric and electronic function for precise dosimetry in the UV‐A and UV‐B regions of the spectrum, and for determination of instantaneous UV exposure levels and skin temperature. The colorimetric chemistry uses (4‐phenoxyphenyl)diphenylsulfonium triflate (PPDPS‐TF) with crystal violet lactone (CVL) and Congo red for UV‐A and UV‐B operation, respectively, when integrated with suitable optical filters. Coatings of poly(ethylene‐vinylacetate) (PEVA) protect the functional materials from sunscreen and other contamination. Quantitative information follows from automated L*a*b* color space analysis of digital images of the devices to provide accurate measurements when calibrated against standard nonwearable sensors. Techniques of screen printing and lamination allow aesthetic designs and integration with epidermal near field communication platforms, respectively. The result is a set of attractive technologies for managing UV exposure at a personal level and on targeted regions of the body.
Multimodal nonlinear optical microscopy is a valuable tool to study complex biological samples. We present an easy-to-operate approach to perform coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence (TPF), second harmonic generation (SHG), and third-harmonic generation (THG) imaging using a single laser source composed of an 80 MHz femtosecond (fs) laser, an optical parametric oscillator (OPO), and a PPLN crystal for frequency doubling. The platform allows vibrationally resonant CARS imaging of CH-rich myelin sheath in fresh spinal tissues and lipid bodies in live cells. Multimodal nonlinear optical imaging and microspectroscopy analysis of fresh liver tissues are demonstrated.
Imaging mass spectrometry allows for the direct investigation of tissue samples to identify specific biological compounds and determine their spatial distributions. Desorption electrospray ionization (DESI) mass spectrometry has been used for the imaging and analysis of rat spinal cord cross sections. Glycerophospholipids and sphingolipids, as well as fatty acids, were detected in both the negative and positive ion modes and identified through tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation and accurate mass measurements. Differences in the relative abundances of lipids and free fatty acids were present between white and gray matter areas in both the negative and positive ion modes. DESI-MS images of the corresponding ions allow the determination of their spatial distributions within a cross section of the rat spinal cord, by scanning the DESI probe across the entire sample surface. Glycerophospholipids and sphingolipids were mostly detected in the white matter, while the free fatty acids were present in the gray matter. These results show parallels with reported distributions of lipids in studies of rat brain. This suggests that the spatial intensity distribution reflects relative concentration differences of the lipid and fatty acid compounds in the spinal cord tissue. The "butterfly" shape of the gray matter in the spinal cord cross section was resolved in the corresponding ion images, indicating that a lateral resolution of better than 200 m was achieved. The selected ion images of lipids are directly correlated with anatomic features on the spinal cord corresponding to the white and the gray
Spinal cord injury (SCI) results in immediate disruption of neuronal membranes followed by extensive secondary neurodegenerative processes. A key approach for repair of SCI is sealing the damaged membranes early. Here we show that axonal membranes injured by compression can be effectively repaired by using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles (60 nm diameter). Injured spinal tissue incubated with micelles showed rapid restoration of compound action potential and reduced calcium influx into axons. Much lower micelle concentration is required for treatment than the positive control, polyethylene glycol. Intravenously injected micelles effectively recovered the locomotor function and reduced the volume and inflammatory response of the lesion in SCI rats. The micelles showed no adverse effects after systemic administration to live rats. Our results suggest that copolymer micelles can interrupt the spread of primary SCI damage with minimal toxicity.
Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation.
Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application.
Exposure to electromagnetic radiation can have a profound impact on human health. Ultraviolet (UV) radiation from the sun causes skin cancer. Blue light affects the body’s circadian melatonin rhythm. At the same time, electromagnetic radiation in controlled quantities has beneficial use. UV light treats various inflammatory skin conditions, and blue light phototherapy is the standard of care for neonatal jaundice. Although quantitative measurements of exposure in these contexts are important, current systems have limited applicability outside of laboratories because of an unfavorable set of factors in bulk, weight, cost, and accuracy. We present optical metrology approaches, optoelectronic designs, and wireless modes of operation that serve as the basis for miniature, low-cost, and battery-free devices for precise dosimetry at multiple wavelengths. These platforms use a system on a chip with near-field communication functionality, a radio frequency antenna, photodiodes, supercapacitors, and a transistor to exploit a continuous accumulation mechanism for measurement. Experimental and computational studies of the individual components, the collective systems, and the performance parameters highlight the operating principles and design considerations. Evaluations on human participants monitored solar UV exposure during outdoor activities, captured instantaneous and cumulative exposure during blue light phototherapy in neonatal intensive care units, and tracked light illumination for seasonal affective disorder phototherapy. Versatile applications of this dosimetry platform provide means for consumers and medical providers to modulate light exposure across the electromagnetic spectrum in a way that can both reduce risks in the context of excessive exposure and optimize benefits in the context of phototherapy.
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