A Fluorescent Carbon Nanoparticle for Photodynamic Cell Therapy via Rapid Non-Endocytic Uptake.

Although photodynamic therapy is a promising approach for cancer treatment, it has limited clinical application due to the poor performance of conventional photosensitizers. In this study, we present a carbon nanoparticle-based photosensitizer for efficient photodynamic cell therapy. The nanoparticles have been synthesized from a steel industry-based waste material, exhibiting strong fluorescence in the visible region, rapidly entering the cell via non-endocytic uptake, and localizing within the mitochondria. Light exposure of nanoparticle-labeled cells offers efficient photodynamic therapy and induces cytotoxicity. Overall, this study highlights the utility of carbon nanoparticles in efficient photodynamic therapy via rapid cellular uptake and subcellular targeting.

Altitude governs the air pollution tolerance and heavy metal accumulation in plants.

Plant response to changing air pollution is a function of various factors including meteorology, type of pollutants, plant species, soil chemistry, and geography. However, the impact of altitude on plant behavior has received little attention to date. A study was therefore conducted to evaluate the impact of altitude on the air pollution tolerance index (APTI), heavy metal accumulation, and deposition in plant species. The results favor the hypothesis of a definite impact of altitude on biochemical and heavy metal accumulation in plants. While a significant decline (p < 0.05) in the relative water content (RWC), APTI, and heavy metal accumulation with increasing altitude was evident in the studied plant species, the behavior of ascorbic acid, leaf extract pH, chlorophyll content, and the particle heavy metal deposition was erratic and did not display any statistically significant differences. The metal accumulation index was in the following order: Ni > Zn > Cu > Pb > Cd > Co. Similarly, the particle heavy metal deposition on the leaf surface (µg/cm2) displayed significant species variability (p < 0.05) and was in the order: Cu (0.303) > Pb (0.301) > Ni (0.269) > Zn (0.241) > Cd (0.044) > Co (0.025). The accumulated heavy metal and RWC showcased a significant positive correlation with the APTI, suggesting the dominant role of RWC in the plant's tolerance against air pollution in an altitudinal gradient. Future studies on the role of micrometeorological conditions in altering APTI may be fruitful in ascertaining these postulations.

On the robustness of multilateration of ionoacoustic signals for localization of the Bragg peak at pre-clinical proton beam energies in water.

Objectives.The energy deposited in a medium by a pulsed proton beam results in the emission of thermoacoustic waves, also called ionoacoustics (IA). The proton beam stopping position (Bragg peak) can be retrieved from a time-of-flight analysis (ToF) of IA signals acquired at different sensor locations (multilateration). This work aimed to assess the robustness of multilateration methods in proton beams at pre-clinical energies for the development of a small animal irradiator.Approach.The accuracy of multilateration performed using different algorithms; namely, time of arrival and time difference of arrival, was investigatedin-silicofor ideal point sources in the presence of realistic uncertainties on the ToF estimation and ionoacoustic signals generated by a 20 MeV pulsed proton beam stopped in a homogeneous water phantom. The localisation accuracy was further investigated experimentally based on two different measurements with pulsed monoenergetic proton beams at energies of 20 and 22 MeV.Main results.It was found that the localisation accuracy mainly depends on the position of the acoustic detectors relative to the proton beam due to spatial variation of the error on the ToF estimation. By optimally positioning the sensors to reduce the ToF error, the Bragg peak could be locatedin-silicowith an accuracy better than 90µm (2% error). Localisation errors going up to 1 mm were observed experimentally due to inaccurate knowledge of the sensor positions and noisy ionoacoustic signals.Significance.This study gives a first overview of the implementation of different multilateration methods for ionoacoustics-based Bragg peak localisation in two- and three-dimensions at pre-clinical energies. Different sources of uncertainty were investigated, and their impact on the localisation accuracy was quantifiedin-silicoand experimentally.

Fabrication and characterization of a multimodal 3D printed mouse phantom for ionoacoustic quality assurance in image-guided pre-clinical proton radiation research.

Objective.Image guidance and precise irradiation are fundamental to ensure the reliability of small animal oncology studies. Accurate positioning of the animal and the in-beam monitoring of the delivered radio-therapeutic treatment necessitate several imaging modalities. In the particular context of proton therapy with a pulsed beam, information on the delivered dose can be retrieved by monitoring the thermoacoustic waves resulting from the brief and local energy deposition induced by a proton beam (ionoacoustics). The objective of this work was to fabricate a multimodal phantom (x-ray, proton, ultrasound, and ionoacoustics) allowing for sufficient imaging contrast for all the modalities.Approach.The phantom anatomical parts were extracted from mouse computed tomography scans and printed using polylactic acid (organs) and a granite/polylactic acid composite (skeleton). The anatomical pieces were encapsulated in silicone rubber to ensure long term stability. The phantom was imaged using x-ray cone-beam computed tomography, proton radiography, ultrasound imaging, and monitoring of a 20 MeV pulsed proton beam using ionoacoustics.Main results.The anatomical parts could be visualized in all the imaging modalities validating the phantom capability to be used for multimodal imaging. Ultrasound images were simulated from the x-ray cone-beam computed tomography and co-registered with ultrasound images obtained before the phantom irradiation and low-resolution ultrasound images of the mouse phantom in the irradiation position, co-registered with ionoacoustic measurements. The latter confirmed the irradiation of a tumor surrogate for which the reconstructed range was found to be in reasonable agreement with the expectation.Significance.This study reports on a realistic small animal phantom which can be used to investigate ionoacoustic range (or dose) verification together with ultrasound, x-ray, and proton imaging. The co-registration between ionoacoustic reconstructions of the impinging proton beam and x-ray imaging is assessed for the first time in a pre-clinical scenario.

Investigating the accuracy of co-registered ionoacoustic and ultrasound images in pulsed proton beams.

The sharp spatial and temporal dose gradients of pulsed ion beams result in an acoustic emission (ionoacoustics), which can be used to reconstruct the dose distribution from measurements at different positions. The accuracy of range verification from ionoacoustic images measured with an ultrasound linear array configuration is investigated both theoretically and experimentally for monoenergetic proton beams at energies relevant for pre-clinical studies (20 and 22 MeV). The influence of the linear sensor array arrangement (length up to 4 cm and number of elements from 5 to 200) and medium properties on the range estimation accuracy are assessed using time-reversal reconstruction. We show that for an ideal homogeneous case, the ionoacoustic images enable a range verification with a relative error lower than 0.1%, however, with limited lateral dose accuracy. Similar results were obtained experimentally by irradiating a water phantom and taking into account the spatial impulse response (geometry) of the acoustic detector during the reconstruction of pressures obtained by moving laterally a single-element transducer to mimic a linear array configuration. Finally, co-registered ionoacoustic and ultrasound images were investigated using silicone inserts immersed in the water phantom across the proton beam axis. By accounting for the sensor response and speed of sound variations (deduced from co-registration with ultrasound images) the accuracy is improved to a few tens of micrometers (relative error less than to 0.5%), confirming the promise of ongoing developments for ionoacoustic range verification in pre-clinical and clinical proton therapy applications.

Synthesis of an industrial by-product-based polymeric additive for use with non-coking coal in metallurgical coke making and a combined density functional theory assessment of its molecular mechanism in fluidity development.

Recently, the utilization of inferior grade coal for the production of fuel-based materials, i.e., metallurgical coke, is an exciting research area in the industrial sector because of the limited reserves of prime coking coal worldwide. In the steel industry, coal tar is the most abundant and sustainable cost-effective by-product, which is a source of an adequate amount of aromatic components such as phenol or its derivative with polycyclic aromatic hydrocarbons. Therefore, for the first time, we developed a novel organic polymeric additive through a cross-linking polymerization technique using a coal-tar precursor and paraformaldehyde monomer with a glycol-tetraline-based plasticizing agent and explored its application for use as inferior coal in metallurgical coke production. Our synthesized polymer was a homogeneous flowable liquid material; the synthesis process was simple, easily scalable with a high production yield (∼90%), and economical. The interaction of the polymeric additive with the coal matrix was investigated via TGA and H2 evolution study to understand the role of the polymer in coal carbonization. The polymeric additive has significantly improved the crucible swelling number (CSN), fluidity, and plastic layer thickness property of coal. In this connection, we also performed a computational study to rationalize the mechanism of action of the polymeric additive. Exploration of the reaction features through density functional theory calculations offered significant insight into the role of the polymer in assisting coal fluidity development. Addition of the polymer prominently enhanced the coke strength after reaction (CSR) of a non-coking coal enriched blend during carbonization. This study discloses new prospects in the steel industry for the sustainable and bulk scale synthesis of a coal tar-based polymeric additive for the profitable production of metallurgical coke.

Enhancement of the ionoacoustic effect through ultrasound and photoacoustic contrast agents.

The characteristic depth dose deposition of ion beams, with a maximum at the end of their range (Bragg peak) allows for local treatment delivery, resulting in better sparing of the adjacent healthy tissues compared to other forms of external beam radiotherapy treatments. However, the optimal clinical exploitation of the favorable ion beam ballistic is hampered by uncertainties in the in vivo Bragg peak position. Ionoacoustics is based on the detection of thermoacoustic pressure waves induced by a properly pulsed ion beam (e.g., produced by modern compact accelerators) to image the irradiated volume. Co-registration between ionoacoustics and ultrasound imaging offers a promising opportunity to monitor the ion beam and patient anatomy during the treatment. Nevertheless, the detection of the ionoacoustic waves is challenging due to very low pressure amplitudes and frequencies (mPa/kHz) observed in clinical applications. We investigate contrast agents to enhance the acoustic emission. Ultrasound microbubbles are used to increase the ionoacoustic frequency around the microbubble resonance frequency. Moreover, India ink is investigated as a possible mean to enhance the signal amplitude by taking advantage of additional optical photon absorption along the ion beam and subsequent photoacoustic effect. We report amplitude increase of up to 200% of the ionoacoustic signal emission in the MHz frequency range by combining microbubbles and India ink contrast agents.