In vivo stealthified molecularly imprinted polymer nanogels incorporated with gold nanoparticles for radiation therapy.

Radiation therapy is a representative therapeutic approach for cancer treatment, wherein the development of efficient radiation sensitizers with low side effects is critical. In this study, a novel stealth radiation sensitizer based on Au-embedded molecularly imprinted polymer nanogels (Au MIP-NGs) was developed for low-dose X-ray radiation therapy. Surface plasmon resonance measurements reveal the good affinity and selectivity of the obtained Au MIP-NGs toward the target dysopsonic protein, human serum albumin. The protein recognition capability of the nanogels led to the formation of the albumin-rich protein corona in the plasma. The Au MIP-NGs acquire stealth capability in vivo through protein corona regulation using the intrinsic dysopsonic proteins. The injection of Au MIP-NGs improved the efficiency of the radiation therapy in mouse models of pancreatic cancer. The growth of the pancreatic tumor was inhibited even at low X-ray doses (2 Gy). The novel strategy reported in this study for the synthesis of stealth nanomaterials based on nanomaterial-protein interaction control shows significant potential for application even in other approaches for cancer treatment, diagnostics, and theranostics. This strategy paves a way for the development of a wide range of effective nanomedicines for cancer therapy.

Biocompatible polymer-modified gold nanocomposites of different shapes as radiation sensitizers.

Radiation therapy is a powerful approach for cancer treatment due to its low invasiveness. The development of radiation sensitizers is of great importance as they assist in providing radiation therapy at a low dose. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-modified gold nanocomposites of different shapes were created using the grafting-to approach to serve as a novel radiation sensitizer with high cellular uptake. The effect of the shape of the nanocomposite on cellular uptake by the breast cancer cell line MCF-7 was also investigated. The PMPC-modified gold nanostars showed the highest cellular uptake compared to the other gold nanocomposites (spheres and rods), whereas cell cytotoxicity was negligible among all candidates. Furthermore, the therapeutic effect of radiation of PMPC-modified nanostars was the highest among all the gold nanocomposites. These results clearly indicate that the shape of the gold nanocomposite is an important parameter for cellular uptake and radiation sensitizing effects in breast cancer cells.

Performance Improvement of EEG-Based BCI Using Visual Feedback Based on Evaluation Scores Calculated by a Computer.

In the study of an electroencephalography (EEG)-based brain computer interface (BCI) using the P300, there have been many reports on computer algorithms that identify the target intended by a user from multiple candidates. However, because the P300 amplitude depends on the subject's condition and is attenuated by physical and mental factors, such as fatigue and motivation, the performance of the BCI is low. Therefore, we aim to improve performance by introducing a feedback mechanism that provides the user with an evaluation calculated by the computer during EEG measurement. In this study, we conducted an experiment in which the user input one character from four characters on the display. By changing the character size according to the evaluation score calculated by the computer, the computer's current evaluation was fed back to the user. This is expected to change the consciousness of the user to enable them to execute a task by knowing the evaluation; that is, if the evaluation is high, the user needs to maintain the current state, and if the evaluation is low, a behavioral change, such as increasing attention, is required to improve the evaluation.As a result of comparing 10 subjects with and without feedback, accuracy improved for seven subjects that were given feedback.

Reduction of the ERP Measurement Time by a Weighted Averaging Using Deep Learning.

In clinical examination, event-related potentials (ERPs) are estimated by averaging across multiple responses, which suppresses background EEG. However, acquiring the number of responses needed for this process is time consuming. We therefore propose a method for shortening the measurement time using weighted-average processing based on the output of deep learning. Using P300 as a representative component, here we focused on the shape of the ERP and evaluated whether our method emphasizes the P300 peak amplitude more than conventional averaging, while still maintaining the waveform shape and the P300 peak latency. Thus, using either CNN or EEGNet, the correlation coefficient reflecting the waveform shape, the peak P300 amplitude, and the peak latency were evaluated and compared with the same factors obtained from conventional waveform averaging. Additionally, the degree of background EEG suppression provided by our method was evaluated using the root mean square of the pre-stimulation waveform, and the number of fewer responses required for averaging (i.e., the reduction in measurement time) was calculated.The results showed that compared with P300 values obtained through conventional averaging, our method allowed for the same shape and response latency, but with a higher amplitude, while requiring a smaller number of responses. Our method showed that by using EEGNet, measurement time could be reduced by 13.7%. This corresponds to approximately a 40-second reduction for every 5 minutes of measurement time.

Molecularly Imprinted Nanogels Possessing Dansylamide Interaction Sites for Controlling Protein Corona In Situ by Cloaking Intrinsic Human Serum Albumin.

Nanomaterials have become increasingly promising for biomedical applications owing to their specific biological characteristics. As drug delivery vehicles, nanomaterials have to circulate in the bloodstream to deliver the encapsulated components to the target tissues. Protein corona regulation is one of the promising approaches that gives stealth capability to avoid immune response. The aim of this study was to develop molecularly imprinted polymer nanogels (MIP-NGs) capable of protein corona regulation, using intrinsic human serum albumin (HSA) and with a functional monomer, dansylamide ethyl acrylamide (DAEAm), the dansylamide group serving as a ligand for HSA. The recognition capability of HSA for MIP-NGs was investigated by isothermal titration calorimetry (ITC). The affinity of the MIP-NGs prepared with DAEAm was then compared to that of the reference MIP-NGs prepared with pyrrolidyl acrylate developed in our previous study. Furthermore, we demonstrated that the concurrent use of these two different functional monomers for molecular imprinting was further effective to construct high-affinity recognition nanocavities for HSA and to form HSA-rich protein corona in the human plasma owing to the different interaction modes of the monomers. We believe that the molecular imprinting strategy developed through the use of ligand-based functional monomer is an effective strategy to create artificial molecular recognition materials.

Molecularly Imprinted Nanogels Capable of Porcine Serum Albumin Detection in Raw Meat Extract for Halal Food Control.

Accurate, simple, and valuable analytical methods for detection of food contamination are rapidly expanding to evaluate the validity of food product quality because of ethnic considerations and food safety. Herein molecularly imprinted nanogels (MIP-NGs), capable of porcine serum albumin (PSA) recognition, were prepared as artificial molecular recognition elements. The MIP-NGs were immobilized on a quartz crystal microbalance (QCM) sensor for detection of pork contamination in real beef extract samples. The MIP-NGs-based QCM sensor showed high affinity and excellent selectivity toward PSA compared to reference serum albumins from five different animals. The high PSA specificity of MIP-NGs led to the detection of pork contamination with a detection limit of 1% (v/v) in real beef extract samples. We believe the artificial molecular recognition materials prepared by molecular imprinting are a promising candidate for halal food control.

Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris.

Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S. epidermidis, from acne patients. A total of 92 and 87 S. epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin-resistant S. epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high-level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256 µg/mL) compared with methicillin-susceptible S. epidermidis strains (2.7%, 3/111 strains) (P < 0.01). The rate of levofloxacin resistance in C. acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S. epidermidis strains (r = 0.93, P < 0.01). The high-level levofloxacin-resistant strains were frequently found in patients with history of quinolone use compared with those without (P < 0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C. acnes but also S. epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.

Gold Nanoparticle-Incorporated Molecularly Imprinted Microgels as Radiation Sensitizers in Pancreatic Cancer.

Radiation therapy is a powerful approach for treating pancreatic cancer, a representative refractory cancer with a high fatality rate, and efforts have been made to decrease the radiation dose and suppress the side effects related to damage to normal tissues during radiation therapy. Gold nanoparticles (Au NPs) are known to possess radiosensitizing activity and low biotoxicity; however, Au NP-incorporated biomaterials have not been investigated as feasible radiosensitizers for use in vivo. Accordingly, in this study, Au NP-incorporated molecularly imprinted polymer microgels (Au-MIP microgels) were created as radiation sensitizers using a newly developed one-pot seeded precipitation polymerization method, and the radiation-sensitizing effects of the Au-MIP microgels were investigated in mice bearing pancreatic tumors. In mice injected with the Au-MIP microgels, tumor sizes were smaller than those in control mice injected with buffer solution when X-ray irradiation was performed. Furthermore, biotoxicity was not observed in mice injected with the Au-MIP microgels because of negligible body weight loss in these mice. Based on these findings, Au-MIP microgels may have applications as novel radiation sensitizers in radiation therapy.

Regulation of spatiotemporal patterning in artificial cells by a defined protein expression system.

Spatiotemporal patterning is a fundamental mechanism for developmental differentiation and homeostasis in living cells. Because spatiotemporal patterns are based on higher-order collective motions of elements synthesized from genes, their behavior dynamically changes according to the element amounts. Thus, to understand life and use this process for material application, creation of artificial cells with time development of spatiotemporal patterning by changes of element levels is necessary. However, realizing coupling between spatiotemporal patterning and synthesis of elements in artificial cells has been particularly challenging. In this study, we established a system that can synthesize a patterning mechanism of the bacterial cell division plane (the so-called Min system) in artificial cells by modifying a defined protein expression system and demonstrated that artificial cells can show time development of spatiotemporal patterning similar to living cells. This system also allows generation and disappearance of spatiotemporal patterning, is controllable by a small molecule in artificial cells, and has the ability for application in cargo transporters. The system developed here provides a new material and a technique for understanding life, development of drug delivery tools, and creation of molecular robots.

Manipulating Living Cells to Construct a 3D Single-Cell Assembly without an Artificial Scaffold.

Artificial scaffolds such as synthetic gels or chemically-modified glass surfaces that have often been used to achieve cell adhesion are xenobiotic and may harm cells. To enhance the value of cell studies in the fields of regenerative medicine and tissue engineering, it is becoming increasingly important to create a cell-friendly technique to promote cell⁻cell contact. In the present study, we developed a novel method for constructing stable cellular assemblies by using optical tweezers in a solution of a natural hydrophilic polymer, dextran. In this method, a target cell is transferred to another target cell to make cell⁻cell contact by optical tweezers in a culture medium containing dextran. When originally non-cohesive cells are held in contact with each other for a few minutes under laser trapping, stable cell⁻cell adhesion is accomplished. This method for creating cellular assemblies in the presence of a natural hydrophilic polymer may serve as a novel next-generation 3D single-cell assembly system with future applications in the growing field of regenerative medicine.