ABSTRACT
Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.
ABSTRACT
INTRODUCTION: Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. METHOD: In this study, a calcium carbonate (CaCO3) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag2S and loaded with l-Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/ML-Arg. RESULTS: Non-invasive US-triggered SDT by Ag2S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). CONCLUSION: Accordingly, the potential of QD@Ca/ML-Arg-was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.
ABSTRACT
Accurate and quick binuclear cell (BC) detection plays a significant role in predicting the risk of leukemia and other malignant tumors. However, manual counting of BCs using microscope images is time consuming and subjective. Moreover, traditional image processing approaches perform poorly due to the limitations in staining quality and the diversity of morphological features in binuclear cell (BC) microscopy whole-slide images (WSIs). To overcome this challenge, we propose a multi-task method inspired by the structure prior of BCs based on deep learning, which cascades to implement BC coarse detection at the WSI level and fine-grained classification at the patch level. The coarse detection network is a multitask detection framework based on circular bounding boxes for cell detection and central key points for nucleus detection. Circle representation reduces the degrees of freedom, mitigates the effect of surrounding impurities compared to usual rectangular boxes and can be rotation invariant in WSIs. Detecting key points in the nucleus can assist in network perception and be used for unsupervised color layer segmentation in later fine-grained classification. The fine classification network consists of a background region suppression module based on color layer mask supervision and a key region selection module based on a transformer due to its global modeling capability. Additionally, an unsupervised and unpaired cytoplasm generator network is first proposed to expand the long-tailed distribution dataset. Finally, experiments are performed on BC multicenter datasets. The proposed BC fine detection method outperforms other benchmarks in almost all evaluation criteria, providing clarification and support for tasks such as cancer screenings.
