BME frontiers最新文献

Sonodynamic therapy (SDT) has emerged as a novel and highly researched advancement in the medical field. Traditional ultrasound contrast agents and novel bubble-shaped agents are used to stimulate cavitation and enhance SDT efficiency. However, the impact of artificially modified shell structures on the acoustic properties of microbubbles remains to be explored. Alternatively, in the absence of bubble-shaped agents, some clinically available organic sonosensitizers and advanced inorganic materials are also used to enhance the efficacy of SDT. Diagnostic and therapeutic ultrasound can also activate cavitation bubbles, which supply energy to sonosensitive agents, leading to the production of cytotoxic free radicals to achieve therapeutic effects. While inorganic materials often spark controversy in clinical applications, their relatively simple structure enables researchers to gain insight into the mechanism by which SDT produces various free radicals. Some organic-inorganic hybrid sonosensitive systems have also been reported, combining the benefits of inorganic and organic sonosensitive agents. Alternatively, by employing cell surface modification engineering to enable cells to perform functions such as immune escape, drug loading, gas loading, and sonosensitivity, cellular sonosensitizers have also been developed. However, further exploration is needed on the acoustic properties, ability to generate reactive oxygen species (ROS), and potential clinical application of this cellular sonosensitizer. This review offers a comprehensive analysis of vesical microbubbles and nanoscale sonocatalysts, including organic, inorganic, combined organic-inorganic sonosensitizers, and cellular sonosensitizers. This analysis will enhance our understanding of SDT and demonstrate its important potential in transforming medical applications.

Objective: We conducted a comprehensive physicochemical analysis of one-dimensional ZnO nanowires (1DZnO), incorporating anti-CYFRA 21-1 immobilization to promote fast optical biomarker detection up to 10 ng ml^-1. Impact Statement: This study highlights the effectiveness of proof-of-concept 1DZnO nanoplatforms for rapid cancer biomarker detection by examining the nanoscale integration of 1DZnO with these bioreceptors to deliver reliable photoluminescent output signals. Introduction: The urgent need for swift and accurate prognoses in healthcare settings drives the rise of sensitive biosensing nanoplatforms for cancer detection, which has benefited from biomarker identification. CYFRA 21-1 is a reliable target for the early prediction of cancer formation that can be perceptible in blood, saliva, and serum. However, 1DZnO nanostructures have been barely applied for CYFRA 21-1 detection. Methods: We assessed the nanoscale interaction between 1DZnO and anti-CYFRA 21-1 antibodies to develop rapid CYFRA 21-1 detection in two distinct matrices: PhosphateBuffered Saline (PBS) buffer and artificial saliva. The chemical modifications were tracked utilizing Fourier transform infrared spectroscopy, while transmission electron microscopy and energy dispersive spectroscopy confirmed antigen-antibody interplay over nanostructures. Results: Our results show high antibody immobilization efficiencies, affirming the effectiveness of 1DZnO nanoplatforms for rapid CYFRA 21-1 testing within a 5-min detection window in both PBS and artificial saliva. Photoluminescence measurements also revealed distinct optical responses across biomarker concentrations ranging from 10 to 1,000 ng ml^-1. Conclusion: Discernible PL signal responses obtained after 5 min affirm the potential of 1DZnO nanoplatforms for further advancement in optical biomarker detection for application in early cancer prognosis.

Objective and Impact Statement: Human epidermal growth factor receptor 2 (HER2) is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer (BC) and helps predict its prognosis. Here, we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in immunohistochemically (IHC) stained BC tissue images. Introduction: Accurate assessment of IHC-stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms. Nevertheless, the traditional workflow of manual examination by board-certified pathologists encounters challenges, including inter- and intra-observer inconsistency and extended turnaround times. Methods: Our deep learning-based method analyzes morphological features at various spatial scales, efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details. Results: This approach addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view, leading to a blind testing classification accuracy of 84.70%, on a dataset of 523 core images from tissue microarrays. Conclusion: This automated system, proving reliable as an adjunct pathology tool, has the potential to enhance diagnostic precision and evaluation speed, and might substantially impact cancer treatment planning.

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF₆)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P-S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P-S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

With the recent advances in neoantigen identification, peptide-based cancer vaccines offer substantial potential in the field of immunotherapy. However, rapid clearance, low immunogenicity, and insufficient antigen-presenting cell (APC) uptake limit the efficacy of peptide-based cancer vaccines. This review explores the barriers hindering vaccine efficiency, highlights recent advancements in synthetic delivery systems, and features strategies for the key delivery steps of lymph node (LN) drainage, APC delivery, cross-presentation strategies, and adjuvant incorporation. This paper also discusses the design of preclinical studies evaluating vaccine efficiency, including vaccine administration routes and murine tumor models.

Spatial monoomics has been recognized as a powerful tool for exploring life sciences. Recently, spatial multiomics has advanced considerably, which could contribute to clarifying many biological issues. Spatial monoomics techniques in epigenomics, genomics, transcriptomics, proteomics, and metabolomics can enhance our understanding of biological functions and cellular identities by simultaneously measuring tissue structures and biomolecule levels. Spatial monoomics technology has evolved from monoomics to spatial multiomics. Moreover, the spatial resolution, high-throughput detection capability, capture efficiency, and compatibility with various sample types of omics technology have considerably advanced. Despite the technological advances in this field, data analysis frameworks have stagnated. Current challenges include incomplete spatial monoomics data analysis pipeline, overly complex data analysis tasks, and few established spatial multiomics data analysis strategies. In this review, we systematically summarize recent developments of various spatial monoomics techniques and improvements in related data analysis pipeline. On the basis of the spatial multiomics technology, we propose a data integration strategy with cross-platform, cross-slice, and cross-modality. We summarize the potential applications of spatial monoomics technology, aiming to provide researchers and clinicians with a better understanding of how such applications have advanced. Spatial multiomics technology is expected to substantially impact biology and precision medicine through measurements of cellular tissue structures and the extraction of biomolecular features.