APL Bioengineering最新文献

{"title":"Identification and regulation of EMT cells <i>in vivo</i> by laser stimulation.","authors":"Xiaohui Zhao, Guang Zhu, Meng Xue, Hao He","doi":"10.1063/5.0268350","DOIUrl":"10.1063/5.0268350","url":null,"abstract":"<p><p>Cells undergoing epithelial-to-mesenchymal transition (EMT) exhibit significant plasticity, making them more tumorigenic, invasive, and stem-like. PLCG2 has been identified as being linked to EMT. Specifically, the PLCG2-high subpopulation of tumor cells shows strong correlations with metastasis. However, it remains unclear whether PLCG2 serves as a direct driver of EMT. In this study, we employ an <i>in vivo</i> photostimulation method using tightly focused femtosecond-laser scanning to activate intracellular Ca²⁺ signaling and induce PLCG2 upregulation. By constructing a subcutaneous tumor model with prostate cancer PC3 cells and single-cell RNA sequencing, we identify distinct cell populations, including cancer stem cells, epithelial tumor cells, proliferating cells, and EMT cells. Upon photostimulation, EMT cells are notably expanded among the primary tumor cells, while epithelial tumor cells decrease in number. During the tumor progression, treatment with a specific PLCG2 inhibitor effectively suppresses the growth of the primary tumor but has no significant impact on metastatic cells. These findings offer valuable insights into the role of PLCG2 in regulating EMT and tumor development.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"026119"},"PeriodicalIF":6.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guest Editorial: Structure and mechanics of biofluids, biomaterials, and biologics.","authors":"E M Furst, F Scheffold, G H McKinley","doi":"10.1063/5.0274572","DOIUrl":"10.1063/5.0274572","url":null,"abstract":"","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 2","pages":"020401"},"PeriodicalIF":6.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis.","authors":"Soraya Hernández-Hatibi, Carlos Borau, Neus Martínez-Bosch, Pilar Navarro, José Manuel García-Aznar, Pedro Enrique Guerrero","doi":"10.1063/5.0242490","DOIUrl":"10.1063/5.0242490","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant tumor-associated stroma composed from pancreatic stellate cells, which play a critical role in tumor progression. Developing accurate <i>in vitro</i> models requires understanding the complex interactions between tumor cells and their microenvironment. In this study, we present a quantitative imaging-based characterization of the three dimensional (3D) self-organization of PDAC tumour spheroids using a microfluidic platform that mimics key aspects of the tumor microenvironment. Our model incorporates collagen type I hydrogels to recreate the extracellular matrix, activated human pancreatic stellate cells (HPSCs), and various tumor cell types. Advanced imaging techniques, including Lattice Lightsheet Microscopy, allowed us to analyze the 3D growth and spatial organization of the spheroids, revealing intricate biomechanical interactions. Our results indicate that alterations in matrix properties-such as stiffness, pore size, and hydraulic permeability-due to variations in collagen concentration significantly influence the growth patterns and organization of PDAC spheroids, depending on tumor subtype and epithelial-mesenchymal phenotype. Higher collagen concentrations promoted larger spheroids in epithelial-like cell lines, while mesenchymal-type cells required increased collagen for self-organization into smaller spheroids. Furthermore, coculture with HPSCs affected spheroid formation distinctly based on each PDAC cell line's genetic and phenotypic traits. HPSCs had opposing effects on epithelial-like cell lines: one cell line exhibited enhanced spheroid growth, while another showed inhibited formation, whereas mesenchymal-like spheroids showed minimal impact. These results provide insights into tumor-stroma interactions, emphasizing the importance of the cell-specific and matrix-dependent factors for advancing our understanding of PDAC progression and informing future therapeutic strategies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016116"},"PeriodicalIF":6.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin.","authors":"Qianqian Du, Qianfan Zhang, Jialing Li, Xiaofei Wang, Xiangyu Gao, Guangyuan Tan, Qian Feng, Jigang Li, Yanchun Meng, Yongsheng Yu","doi":"10.1063/5.0256571","DOIUrl":"10.1063/5.0256571","url":null,"abstract":"<p><p>Breast cancer remains a significant global health challenge, emphasizing the pressing need for innovative therapeutic approaches. Our thorough research investigates the potential of mesoporous polydopamine nanoparticles (MPDA) as a targeted treatment for breast cancer. Meticulously crafted, these nanoparticles were loaded with honokiol (HK), which is a natural product, and then coated with functionalized hyaluronic acid (HA) to boost their ability to target breast cancer cells that overexpress CD44 receptors. The deep penetrating and photothermal (PTT) composite nanosystem combined with low-dose metformin (Met) improves the efficacy of synergetic therapy against breast tumors. The designed nanosystem exhibited exceptional biocompatibility and stability, suggesting its suitability for therapeutic use. Our <i>in vitro</i> studies demonstrated that the nanosystem precisely targeted and penetrated breast cancer cells, resulting in significant cell death. Additionally, <i>in vivo</i> studies showed that the nanosystem markedly inhibited tumor growth compared to the control group. This tumor-inhibiting effect was due to the combined action of the encapsulated HK, free Met, and the photothermal effect induced by near-infrared laser irradiation. This combination potently stimulates the expression of cleaved caspase-3 and cleaved PARP proteins, ultimately triggering cell apoptosis and effectively curbing tumor proliferation. Our research not only underscores the promising potential of nanoparticles for targeted breast cancer therapy but also sets the stage for further exploration and development of novel nanomedicine-based therapeutic strategies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016115"},"PeriodicalIF":6.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in nanotechnology for targeting cancer-associated fibroblasts: A review of multi-strategy drug delivery and preclinical insights.","authors":"Zhongsong Zhang, Yujie Tang, Dan Luo, Jing Qiu, Long Chen","doi":"10.1063/5.0244706","DOIUrl":"https://doi.org/10.1063/5.0244706","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment by promoting tumor growth, immune evasion, and metastasis. Recently, drug delivery systems targeting CAFs have emerged as a promising long-term and effective approach to cancer treatment. Advances in nanotechnology, in particular, have led to the development of nanomedicine delivery systems designed specifically to target CAFs, offering new possibilities for precise and personalized cancer therapies. This article reviews recent progress in drug delivery using nanocarriers that target CAFs. Additionally, we explore the potential of combining multiple therapies, such as chemotherapy and immunotherapy, with nanocarriers to enhance efficacy and overcome drug resistance. Although many preclinical studies show promise, the clinical application of nanomedicine still faces considerable challenges, especially in terms of drug penetration and large-scale production. Therefore, this review aims to provide a fresh perspective on CAF-targeted drug delivery systems and highlight potential future research directions and clinical applications.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"011502"},"PeriodicalIF":6.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable photosensitive bone cement enhancing angiogenesis and osteogenic differentiation for the treatment of bone nonunion.","authors":"Mengnan Wen, Xueqiang Guo, Yan Gong, Fei Xue, Zhenlin Fan, Zhanting Kang, Jixiang Li, Lei Wang, Xiansong Wang, Wenjie Ren","doi":"10.1063/5.0246207","DOIUrl":"10.1063/5.0246207","url":null,"abstract":"<p><p>Nonunion fractures present a significant clinical challenge because of their complex microenvironment, which includes poor vascularization, insufficient osteogenesis, infection, and separation of fracture ends. The current clinical treatments have certain limitations. Inspired by this phenomenon, sandcastle worms secrete adhesive proteins that bind sand grains, shell fragments, and mineral particles, thereby constructing their \"castles.\" In this study, we developed an injectable bone cement using methacryloyl chitosan (CSMA) combined with a specific concentration of oyster shell nanoparticles (OS-np) to treat nonunion fractures. Oyster shells are composed primarily of calcium carbonate, which releases ions that promote angiogenesis and osteogenesis. The <i>in vivo</i> results at 8 weeks showed that the expression of BMP2, RUNX2, and VEGF in the OS-np/CSMA group was increased by 5.47, 4.38, and 3.54 times, respectively, compared to the control group, significantly enhancing vascularization and bone repair in the bone nonunion model. The injectability of the OS-np/CSMA bone cement ensures that it can adapt well to the complex structures of nonunion sites, providing a supportive matrix for new bone formation. Both <i>in vivo</i> and <i>in vitro</i> osteogenesis experiments demonstrated that the OS-np/CSMA bone cement significantly enhanced vascularization and bone repair in nonunion models, which was because of the synergistic effects of ion release and the bioactive properties of the oyster shell nanoparticles. This study highlights the potential of OS-np/CSMA injectable bone cement as a promising treatment strategy for complex nonunion fractures that effectively promotes angiogenesis and osteogenesis.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016114"},"PeriodicalIF":6.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualization of the hatching of brine shrimp eggs using ultrafast and high-resolution phase-contrast CTs.","authors":"Rongbiao Tang, Yanan Fu, Ke Li, Feixiang Wang, Ke-Min Chen","doi":"10.1063/5.0238482","DOIUrl":"10.1063/5.0238482","url":null,"abstract":"<p><p>Micro and small organisms (MSOs) are essential components of the ecosystem. Many MSOs reproduce by hatching eggs, making it crucial to study the morphology of these eggs and their incubation products (IPs) in related research. Phase-contrast CT (PCCT) is a powerful imaging modality known for its high resolution and sensitivity to soft tissues. In this study, an ultrafast PCCT system was used to scan brine shrimp eggs (BSEs) before hatching to determine their viability. High-resolution PCCT was used to reveal the microstructures of BSEs and IPs. We found that normal BSEs have an exclusively regular structure, making them easily identifiable. The use of ultrafast PCCT not only allowed for quick determination of BSE viability but also significantly reduced the amount of irradiation exposure to the eggs. All of the normal BSEs that were tested successfully hatched into brine shrimp, demonstrating the high safety of ultrafast PCCT. The high-resolution PCCT images clearly showed the formation of hatching membranes, cracks, and deformable bodies during the hatching process. The results suggest that ultrafast PCCT has the potential to assess the viability of MSO eggs, while high-resolution PCCT can provide valuable insight into the morphological changes that occur during the hatching process.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016113"},"PeriodicalIF":6.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCBP2 promotes immune evasion via cGAS-STING pathway in biochemical recurrence of prostate cancer.","authors":"Zeng Zhou, Tiewen Li, Yichen Zhang, Xuehao Zhou, Xiaodong Song, Shiyu Ji, Yishu Huang, Yu Zhang, Yuan Ruan","doi":"10.1063/5.0250173","DOIUrl":"10.1063/5.0250173","url":null,"abstract":"<p><p>Immunotherapy resistance is a significant obstacle in the treatment of prostate cancer (PCa), primarily due to immune evasion mechanisms. This study aims to explore cancer-intrinsic immune evasion-related genes (CIERGs) in PCa and develop a predictive signature for biochemical recurrence (BCR). Bulk RNA-seq data and single-cell RNA-sequencing (scRNA-seq) were obtained from TCGA and Gene Expression Omnibus database. The scRNA-seq data analysis revealed higher immune evasion scores in tumor cells compared to normal cells. Differentially expressed genes from TCGA-PRAD and GSE70769 cohorts were intersected with 182 core immune evasion genes, followed by univariate Cox regression, identifying 48 CIERGs significantly associated with BCR. Nonnegative matrix factorization (NMF) clustering revealed two immune evasion-related PCa subtypes. A risk signature based on CIERGs was developed using LASSO regression, and a nomogram was created to predict BCR-free survival. Among the 48 identified CIERGs, poly(C)-binding protein 2 (PCBP2) emerged as a key risk factor associated with poor prognosis in PCa, and its function was validated <i>in vitro</i>. NMF clustering identified two subtypes, with the C1 subtype having a poorer prognosis. Gene Set Variation Analysis highlighted enrichment in cell cycle, extracellular matrix receptor interaction, and transforming growth factor-beta signaling pathways in the C1 subtype. A CIERGs-based risk signature, including six key genes, was developed and validated, with the nomogram showing high predictive accuracy. <i>In vitro</i> experiments showed PCBP2 promotes PCa cell proliferation, migration, and invasion by inhibiting the cyclic GMP-AMP synthase-STING pathway. The CIERGs signature provides a precise prediction of BCR, with PCBP2 emerging as a potential therapeutic target due to its inhibition of the cGAS-STING pathway in PCa.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016112"},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrodynamic efficient cell capture and pairing method on microfluidic cell electrofusion chip.","authors":"Xuefeng Wang, Yaqi Bai, Xiaoling Zhang, Wei Li, Jun Yang, Ning Hu","doi":"10.1063/5.0250472","DOIUrl":"10.1063/5.0250472","url":null,"abstract":"<p><p>Cell fusion is a widely employed process in various biological procedures, demonstrating significant application value in biotechnology. Cell pairing is a crucial manipulation for cell fusion. Standard fusion techniques, however, often provide poor and random cell contact, leading to low yields. In this study, we present a novel microfluidic device that utilizes a three-path symmetrical channel hydrodynamic capture method to achieve high-efficiency cell capture and pairing. The device contains several symmetrical channels and capture units, enabling three-path capture of two kinds of cells. To better understand the conditions necessary for effective cell pairing, we established a theoretical model of the three-path trapping flow field and conducted a qualitative force analysis on cells. Using K562 cells to explore the effect of different volumetric flow ratios of symmetric channels on cell capture and pairing efficiency, we finally got the optimized structure and obtained a single-cell capture efficiency of approximately 95.6 ± 2.0% and a cell pairing efficiency of approximately 83.3 ± 8.8%. Subsequently, electrofusion experiments were carried out on the paired cells, resulting in a fusion efficiency of approximately 77.8 ± 9.6%.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016111"},"PeriodicalIF":6.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenine base editing rescues pathogenic phenotypes in tissue engineered vascular model of Hutchinson-Gilford progeria syndrome.","authors":"Nadia O Abutaleb, Xin D Gao, Akhil Bedapudi, Leandro Choi, Kevin L Shores, Crystal Kennedy, Jordyn E Duby, Kan Cao, David R Liu, George A Truskey","doi":"10.1063/5.0244026","DOIUrl":"10.1063/5.0244026","url":null,"abstract":"<p><p>The rare, accelerated aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is commonly caused by a <i>de novo</i> c.1824 C > T point mutation of the <i>LMNA</i> gene that results in the protein progerin. The primary cause of death is a heart attack or stroke arising from atherosclerosis. A characteristic feature of HGPS arteries is loss of smooth muscle cells. An adenine base editor (ABE7.10max) corrected the point mutation and produced significant improvement in HGPS mouse lifespan, vascular smooth muscle cell density, and adventitial fibrosis. To assess whether base editing correction of human HGPS tissue engineered blood vessels (TEBVs) prevents the HGPS vascular phenotype and to identify the minimum fraction of edited smooth muscle cells needed to effect such changes, we transduced HGPS iPSCs with lentivirus containing ABE7.10max. Endothelial cells (viECs) and smooth muscle cells (viSMCs) obtained by differentiation of edited HGPS iPSCs did not express progerin and had double-stranded DNA breaks and reactive oxygen species at the same levels as healthy viSMCs and viECs. Editing HGPSviECs restored a normal response to shear stress. Normal vasodilation and viSMC density were restored in TEBVs made with edited cells. When TEBVs were prepared with at least 50% edited smooth muscle cells, viSMC proliferation and myosin heavy chain levels significantly improved. Sequencing of TEBV cells after perfusion indicated an enrichment of edited cells after 5 weeks of perfusion when they comprised 50% of the initial number of cells in the TEBVs. Thus, base editing correction of a fraction of HGPS vascular cells improves human TEBV phenotype.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"9 1","pages":"016110"},"PeriodicalIF":6.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}