Application and Development of Cell Membrane Functionalized Biomimetic Nanoparticles in the Treatment of Acute Ischemic Stroke.

Ischemic stroke is a serious neurological disease involving multiple complex physiological processes, including vascular obstruction, brain tissue ischemia, impaired energy metabolism, cell death, impaired ion pump function, and inflammatory response. In recent years, there has been significant interest in cell membrane-functionalized biomimetic nanoparticles as a novel therapeutic approach. This review comprehensively explores the mechanisms and importance of using these nanoparticles to treat acute ischemic stroke with a special emphasis on their potential for actively targeting therapies through cell membranes. We provide an overview of the pathophysiology of ischemic stroke and present advances in the study of biomimetic nanoparticles, emphasizing their potential for drug delivery and precision-targeted therapy. This paper focuses on bio-nanoparticles encapsulated in bionic cell membranes to target ischemic stroke treatment. It highlights the mechanism of action and research progress regarding different types of cell membrane-functionalized bi-onic nanoparticles such as erythrocytes, neutrophils, platelets, exosomes, macrophages, and neural stem cells in treating ischemic stroke while emphasizing their potential to improve brain tissue's ischemic state and attenuate neurological damage and dysfunction. Through an in-depth exploration of the potential benefits provided by cell membrane-functionalized biomimetic nanoparticles to improve brain tissue's ischemic state while reducing neurological injury and dysfunction, this study also provides comprehensive research on neural stem cells' potential along with that of cell membrane-functionalized biomimetic nanoparticles to ameliorate neurological injury and dysfunction. However, it is undeniable that there are still some challenges and limitations in terms of biocompatibility, safety, and practical applications for clinical translation.

Automated detection of nine infantile fundus diseases and conditions in retinal images using a deep learning system.

Purpose: We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and health conditions to satisfy urgent needs of ophthalmologists. Methods: We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results. Results: Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62% (95% CI, 94.34%-94.90%), 94.07% (95% CI, 93.32%-94.82%), 90.56% (95% CI, 88.64%-92.48%), 92.34% (95% CI, 91.87%-92.81%), 91.15% (95% CI, 90.37%-91.93%), and 99.08% (95% CI, 99.07%-99.09%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45% (95% CI, 96.37%-96.53%), 95.86% (95% CI, 94.56%-97.16%), 94.37% (95% CI, 93.95%-94.79%), 95.03% (95% CI, 94.45%-95.61%), 94.43% (95% CI, 93.96%-94.90%), and 99.51% (95% CI, 99.51%-99.51%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities. Conclusions: IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM / 3PM) in the treatment of infantile fundus diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00350-y.

Chorioretinal venous anastomosis for non-ischemic retinal vein occlusion.

Retinal vein occlusion (RVO) refers to the occlusion of the central retinal vein or primary and secondary branches caused by multiple factors. Clinical treatments for it include intravitreal or systemic vasodilator application, local usage of steroids and NSAID (non-steroidal anti-inflammatory drugs), thrombolysis, hemodilution, retinal laser photocoagulation, vitrectomy with vascular sheath incision, chorioretinal venous anastomosis (CRVA), and so on. At present, most treatments are aimed at RVO complications, while chorioretinal vein anastomosis can fundamentally reflux retinal vein blood through the choroid by venous vascular remodeling. Reports on the treatment of retinal vein occlusion by chorioretinal anastomosis are numerous in various countries. As a treatment means, CRVA can drain the venous blood, skipping the thrombosis spot, thus partially relieving anatomical vascular occlusion to achieve a therapeutic purpose. In this study, CRVA is evaluated from the aspects of indications, implementation process, postoperative effect evaluation, complications, and combination with anti-VEGF treatment. Based on the development of laser technology and vitrectomy, we hope to further review this treatment and provide a new reference for the clinical treatment of RVO.

Flagellated Janus particles for multimodal actuation and transport.

Catalytic Janus particles rely on chemical decomposition to self-propel and have displayed enormous potential for targeted drug delivery and cellular penetration. Catalytic propulsion mechanisms are limiting, however, with fuel requirements and specialized fluid properties being necessary to achieve propulsion. We have improved the dynamic propulsion of catalytic Janus particles by functionalizing flagellar filaments to one of their hemispheres. Flagellated Janus particles, torqued by rotating magnetic fields, swim along their rotation axis using the explicit chirality and flexibility of flagella, mimicking flagellar rotation of live bacteria. Depending on the working fluid, flagellated Janus particles can propel using either catalytic or swimming propulsion. We demonstrate experimentally that flagellated Janus particles behave predictably under the two actuation modes and can precisely follow trajectories under closed-loop feedback control. Flagellated Janus particles were demonstrated to swim in both Newtonian and shear-thickening fluids. These are the first Janus particles developed that can be propelled interchangeably between catalytic and flagellar swimming propulsion, allowing two distinct propulsion mechanisms for future use within in vivo operations.

Flagellar nanorobot with kinetic behavior investigation and 3D motion.

Wirelessly controlled nanorobots have the potential to perform highly precise maneuvers within complex in vitro and in vivo environments. Flagellar nanorobots will be useful in a variety of biomedical applications, however, to date there has been little effort to investigate essential kinetic behavior changes related to the geometric properties of the nanorobot and effects imparted to it by nearby boundaries. Flagellar nanorobots are composed of an avidin-coated magnetic nanoparticle head (MH) and a single biotin-tipped repolymerized flagellum that are driven by a wirelessly generated rotating magnetic field. Nanorobots with different MHs and flagellar lengths were manually guided to perform complex swimming trajectories under both bright-field and fluorescence microscopy visualizations. The experimental results show that rotational frequency, handedness of rotation direction, MH size, flagellar length, and distance to the bottom boundary significantly affect the kinematics of the nanorobot. The results reported herein summarize fundamental research that will be used for the design specifications necessary for optimizing the application of helical nanorobotic devices for use in delivery of therapeutic and imaging agents. Additionally, robotic nanoswimmers were successfully navigated and tracked in 3D using quantitative defocusing, which will significantly improve the efficiency, function, and application of the flagellar nanorobot.

Heterogeneously flagellated microswimmer behavior in viscous fluids.

An analysis of heterogeneously flagellated microswimmers inside viscous fluids is presented. Flagella harvested from Salmonella typhimurium were isolated, repolymerized, and functionalized to have biotin at their ends, allowing for chemical attachment along the surfaces of avidin-coated microparticles. Assembled microswimmers were rotated under incremental magnetic field frequencies, in saline and methylcellulose solutions, to baseline their velocity responses. A mean square displacement analysis revealed that rotating microswimmers exhibited anomalous diffusive behavior at small time scales in each fluid and had increased diffusivity compared with the non-rotating cases. Flagellated microswimmers had decreased diffusivity when compared with non-flagellated microparticles in Brownian conditions. Microswimmers were demonstrated to perform selected trajectories under proportional feedback control with reasonable accuracy. Finally, microswimmer propulsion was shown to be heavily influenced by the handedness of the rotating magnetic fields, with frequency induced reversals of swimming direction observed under clockwise rotation; this effect was determined to be the result of flagellar bundling and unbundling.

Characterization of Flagellar Filaments and Flagellin through Optical Microscopy and Label-Free Nanopore Responsiveness.

In this study, we investigated the translocation characteristics of flagellar filaments (Salmonella typhimurium) and flagellin subunits through silicon nitride nanopores in tandem with optical microscopy analysis. Even though untagged flagella are dark to the optical method, the label-free nature of the nanopore sensor allows it to characterize both tagged (Cy3) and pristine forms of flagella (including real-time developments). Flagella were depolymerized to flagellin subunits at ∼65 °C (most commonly reported temperature), ∼70 °C, ∼75 °C, and ∼80 °C to investigate the effect of temperature (Tdepol) on depolymerization. The change in conductance (ΔG) profiles corresponding to Tdepol ∼65 °C and ∼70 °C were bracketed within the flagellin monomer profile whereas those of ∼75 °C and ∼80 °C extended beyond this profile, suggesting a change to the native protein state. The molecular radius calculated from the excluded electrolyte volume of flagellin through nanopore-based ΔG characteristics for each Tdepol of ∼65 °C, ∼70 °C, ∼75 °C, and ∼80 °C yielded ∼4.2 ± 0.2 nm, ∼4.3 ± 0.3 nm, ∼4.1 ± 0.2 nm, and ∼4.7 ± 0.5 nm, respectively. This, along with ΔG (plateaued values) and translocation time profiles, points to the possibility of flagellin misfolding at ∼80 °C.