Materials Today Bio最新文献

{"title":"Dynamic multistage nanozyme hydrogel reprograms diabetic wound microenvironment: synergistic oxidative stress alleviation and mitochondrial restoration","authors":"Jingyu Yan ,&nbsp;Yifan Zhao ,&nbsp;Chenying Cui ,&nbsp;Lihong Zhou ,&nbsp;Yurong Xu,&nbsp;Ziyang Bai,&nbsp;Kaifang Zhang,&nbsp;Jiahui Tong,&nbsp;Yingyu Liu,&nbsp;Lingxiang Sun,&nbsp;Meijun Du,&nbsp;Yanling Mi,&nbsp;Xing Wang,&nbsp;Xiuping Wu,&nbsp;Bing Li","doi":"10.1016/j.mtbio.2025.101780","DOIUrl":"10.1016/j.mtbio.2025.101780","url":null,"abstract":"<div><div>Chronic diabetic wounds remain a significant clinical challenge due to persistent bacterial infections, oxidative stress, impaired angiogenesis, and mitochondrial dysfunction. Traditional therapies often fail to address these interrelated pathological factors, highlighting the urgent need for innovative solutions. Here, we present a Mn-ZIF@GOx/BC (MZGB) hydrogel system, where Mn-ZIF@GOx (MZG) nanozymes are successfully integrated into a bacterial cellulose (BC) hydrogel via hydrogen bonding and electrostatic interactions. The MZGB hydrogel lowers wound pH by oxidizing excess glucose into gluconic acid. It exhibits strong ROS scavenging capabilities through its superoxide dismutase and catalase-like activities, while simultaneously providing oxygen. By restoring redox homeostasis, it protects mitochondrial function and enhances cellular energy metabolism. By reprogramming macrophages, MZGB creates a favorable immune microenvironment, significantly promoting angiogenesis through paracrine mechanisms. This facilitates cell-to-cell communication, forming a positive feedback loop. Moreover, MZGB demonstrates ROS-independent antibacterial properties. BC hydrogel ensures adhesion and moisture regulation, forming a protective barrier and maintaining an optimal wound environment. This multifunctional hydrogel represents a promising nanotherapeutic approach for efficiently treating diabetic wounds by precisely regulating the wound microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101780"},"PeriodicalIF":8.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane biomimetic nanoenzyme-incorporated hybrid glycyrrhizic acid hydrogel for precise mitochondrial ROS scavenging for osteoarthritis treatment","authors":"Yong Fan ,&nbsp;Zexuan Niu ,&nbsp;Li Yin ,&nbsp;Longtao Yao ,&nbsp;Sheyuan Ding ,&nbsp;Yu Tong ,&nbsp;Jiao Wang ,&nbsp;Zheping Hong ,&nbsp;Jihang Chen ,&nbsp;Qiong Zhang ,&nbsp;Lichen Ji ,&nbsp;Jiaxin Chen ,&nbsp;Chen Xia ,&nbsp;Qing Bi","doi":"10.1016/j.mtbio.2025.101778","DOIUrl":"10.1016/j.mtbio.2025.101778","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive degenerative disorder which severely threatens the quality of life of older individuals. OA progression is closely related to heightened levels of mitochondrial reactive oxygen species (mtROS). Although nanozymes have a good ROS-scavenging effect, they cannot precisely scavenge mtROS because of the immune rejection of cell membranes, lysosomal escape, and the inability of conventional nanozymes to directly target mitochondria. Dual-target nanozymes were engineered to precisely scavenge mtROS in chondrocytes. We used chondrocyte membrane-camouflaged TPP-modified hollow Prussian blue nanozymes and subsequently encapsulated these nanozymes in a hybrid glycyrrhizic acid hydrogel. The therapeutic efficacy and underlying mechanisms were assessed in vitro and in vivo. The novel nanozymes enhanced cell selectivity, immune evasion capabilities, and mitochondrial targeting. The dual-targeted nanozymes exerted a pronounced therapeutic impact on inflammatory chondrocytes, mitigated mtDNA leakage by precisely scavenging mtROS, dampened cGAS-STING-NF-κB signaling, and enhanced chondrocyte function. The hybrid hydrogels also exhibited improved therapeutic outcomes. We confirmed the beneficial effects of the nanozyme-hydrogel combination on OA progression in mice. The nanozyme-hydrogel combination can reduce precisely scavenge mtROS in chondrocytes, avoiding the leakage of mtDNA and suppressing the cGAS-STING-NF-κB signaling pathway, thereby decreasing inflammatory responses and alleviate OA progression.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101778"},"PeriodicalIF":8.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifunctional MXene quantum dots-coated bimetallic Prussian blue analogues for sensitive sensing and accurate localization imaging of miRNAs in living cells","authors":"Qiannan You ,&nbsp;Panyong Wang ,&nbsp;Tongtong Zhu ,&nbsp;Zixuan Jia ,&nbsp;Zhimin Chang ,&nbsp;Li Li ,&nbsp;Wen-Fei Dong","doi":"10.1016/j.mtbio.2025.101747","DOIUrl":"10.1016/j.mtbio.2025.101747","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are involved in multiple cellular processes and play a critical role in clinical diagnosis. In-situ spatiotemporal imaging of miRNAs in living cells is tightly linked to the carcinogenesis and development of malignant tumors. Herein, we proposed a bifunctional nanosystem-based MXene quantum dots-coated bimetallic Prussian blue analogues (Co-Mn PBA@MQDs) to execute in-vitro sensing and intracellular imaging of miRNA in living cells. The 3D nanostructures of Co-Mn PBAs were regulated to slow down the coordination reaction rate by controlling the diffusion of metal clusters and ligand precursors, thereby anchoring MQDs as the carriers of DNA probes. The resulting Co-Mn PBA@MQDs nanoparticles with miRNA recognition ability exhibit excellent electrocatalytic and photoluminescence properties for target miRNA analysis. It reached miRNA detection limit of 0.37 fM (S/N = 3) with a wide linear range of 1 fM to 1 nM, and allowed distinguish family members without additional complex modifications. Meanwhile, DNA probe adsorbed on Co-Mn PBA@MQDs can provide delivery capacity for intracellular miRNA location, resulting in the in-situ monitoring and imaging of miRNA with deregulated expression levels in cancer cells. With these advantages, the developed strategy provides a paradigm for the rational design of the miRNA analysis system, which is expected to be widely applied to disease diagnosis and further theragnostic fields.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101747"},"PeriodicalIF":8.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A carbon nanotube/pyrrolidonecarboxylic acid zinc sponge for programmed management of diabetic wounds: Hemostatic, antibacterial, anti-inflammatory, and healing properties","authors":"Chenwei Wu ,&nbsp;Bo Liu ,&nbsp;Qiulan Wen ,&nbsp;Qiliang Zhai","doi":"10.1016/j.mtbio.2025.101769","DOIUrl":"10.1016/j.mtbio.2025.101769","url":null,"abstract":"<div><div>Wound healing in patients with diabetes is challenging because of chronic inflammation, inadequate vascularization, and susceptibility to infection. Current wound dressings often target specific stages of healing and lack comprehensive therapeutic approaches. This study introduces a novel approach using a photodetachable sponge scaffold incorporating carbon nanotubes (CNTs), known for their high photothermal conversion efficiency, electrical conductivity, and water absorption properties. The scaffold incorporated pyrrolidonecarboxylic acid zinc (PC₁Z₂), a compound with anti-inflammatory and moisturizing properties, which was cross-linked within a network of CNTs and a decellularized dermal matrix. The resulting shape-memory sponge scaffold actively interfaces with endogenous electric fields, facilitating electrical signal transmission to skin cells and accelerating tissue repair. Upon exposure to near-infrared (NIR) light, the PC₁Z₂ scaffold enhanced antibacterial efficacy (98 %) through photothermal conversion, promoting tissue metabolism at the wound site. Notably, the scaffold absorbed wound exudates and gradually released Zn²⁺, effectively reducing chronic inflammation in the mice. In a diabetic rat wound model, the PC₁Z₂ scaffold absorbed exudates, reduced inflammation, and accelerated granulation tissue formation, wound angiogenesis, and re-epithelialization. This innovative PC₁Z₂ sponge dressing shows promise for enhancing the healing of diabetic wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101769"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organoid in droplet: Production of uniform pancreatic cancer organoids from single cells","authors":"Haitao Liu ,&nbsp;Tingting Tao ,&nbsp;Zhongqiao Gan ,&nbsp;Yingying Xie ,&nbsp;Yaqing Wang ,&nbsp;Yizhao Yang ,&nbsp;Xu Zhang ,&nbsp;Xianliang Li ,&nbsp;Jianhua Qin","doi":"10.1016/j.mtbio.2025.101765","DOIUrl":"10.1016/j.mtbio.2025.101765","url":null,"abstract":"<div><div>Cancer organoids have improved our understanding of recapitulating the histology, genotypes, and drug response of patient tumors for personalized medicine. However, the existing cancer organoids are typically grown in animal-derived matrices (e.g., Matrigel), which suffer from poor reproducibility and low throughput due to uncontrollable origin of seed cells, undefined matrix, and manual manipulation. Here, we report a new strategy to massively generate uniform pancreatic cancer organoids (PCOs) in a droplet system from single cells. This system is composed of all-in-water fluids that allow to mildly encapsulate single tumor cell into isolated droplet, which subsequently proliferate and self-assemble into organoids, resembling the initial state of a tumor in the body. This high-throughput method can produce thousands of organoids in a single batch. The droplets can serve as templates for synthesizing defined microgels with proper stiffness similar to that of native tumors, facilitating functional expressions of PCOs. These organoids exhibit superior uniformity and controllability in terms of size and morphologies compared with organoids cultured in manually dropped Matrigel, due mainly to the controllable number of initiating cells and defined microgels. In addition, the established organoids maintain the key biomarkers of pancreatic tumor (e.g., KRT7, KRT19 and SOX9) and higher expression of genes associated with drug metabolism confirmed by RNA-seq and PCR analysis. Furthermore, they show distinguishing responses to four clinically used drugs in a reproducible manner in automatic pipetting workstation, indicating the feasibility of the proposed method in high-throughput drug testing. The established strategy has integrated the formation, 3D cultures, and analysis of PCOs derived from single cells in a whole system, which may provide a novel platform for advancing organoids research with standardized procedure in translational applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101765"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A microfluidic electrochemical immunosensor for detection of CEA and Ki67 in 3D tumor spheroids","authors":"Sujin Kim ,&nbsp;Seonyeop Kim ,&nbsp;Chanjin Ko ,&nbsp;Wonseok Lee ,&nbsp;Hwan Drew Kim","doi":"10.1016/j.mtbio.2025.101768","DOIUrl":"10.1016/j.mtbio.2025.101768","url":null,"abstract":"<div><div>Microfluidic chip-based electrochemical sensors have been developed to detect cancer biomarkers and monitor changes in the tumor microenvironment. However, the limitation of detecting only a single biomarker restricts their utility as accurate diagnostic tools. Simultaneous detection of multiple tumor biomarkers is important for early diagnosis of cancer. In this work, we report the development of a microfluidic-based electrochemical immunosensor platform capable of simultaneously observing multiple biomarkers expressed by three dimensions (3D) cell spheroids. The sensor platform employs a nanocomposite electrode material consisting of gold nanoparticles and carbon nanotubes, which enables sensitive and selective detection. The sensor was fabricated using 3D and printed circuit boards (PCB) printing techniques, demonstrating the feasibility of cost-effective manufacturing. The developed platform was able to quantitatively detect two key cancer biomarkers, carcinoembryonic antigen (CEA) and Ki67, with limits of detection of 0.97 ng/mL for each. Furthermore, the sensor was successfully utilized to observe the knockdown of these biomarkers, showcasing its potential for both diagnostic and therapeutic monitoring applications. These results suggest that the presented electrochemical sensor platform provides a promising lab-on-a-chip technology for comprehensive 3D cell spheroid-based cancer biomarker analysis, which could have significant implications for future clinical diagnostics and personalized medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101768"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdermal delivery of timolol maleate using hydrogel microneedles for the treatment of infantile haemangiomas","authors":"Xiaokun Lin ,&nbsp;Tongshuai Kuang ,&nbsp;Lei Wang ,&nbsp;Wei Cai ,&nbsp;Linxing Yang ,&nbsp;Changrong Guo ,&nbsp;Xinyang Pan ,&nbsp;Yuanhao Wang ,&nbsp;Qiang Gao ,&nbsp;Kaihui Nan ,&nbsp;Lingli Li","doi":"10.1016/j.mtbio.2025.101752","DOIUrl":"10.1016/j.mtbio.2025.101752","url":null,"abstract":"<div><div>Infantile haemangioma (IH), the most prevalent vascular tumour in infants, requires early intervention because of the potential complications in critical areas such as the head and face. Current treatments, including topical timolol maleate (TIM), face challenges such as poor compliance, low drug utilisation, and lengthy treatment durations. In this study, we developed a hydrogel microneedle (MN) using photocurable bovine serum albumin methacryloyl (BSAMA) as a carrier for TIM. Our results showed the controlled release of TIM from BSAMA-TIM MNs, with approximately 69 % release ratio within 72 h. <em>In-vivo</em> studies on nude mice demonstrated that BSAMA-TIM-MNs inhibited the growth of haemangioma xenografts. Our TIM-delivering MNs exhibited high therapeutic efficacy, minimal cytotoxicity, and reduced dosing frequency. In conclusion, BSAMA-TIM MNs provide a promising strategy for treating IH.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101752"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed β-TCP scaffold as a bone-mimicking environment for an engineered model of osteosarcoma: In vitro properties and transcriptomic insights","authors":"Ksenia Menshikh ,&nbsp;Virginia Alessandra Gobbo ,&nbsp;Mauro Nascimben ,&nbsp;Markus Hannula ,&nbsp;Andrea Cochis ,&nbsp;Tiziano Serra ,&nbsp;Jonathan Massera ,&nbsp;Abhay Pandit ,&nbsp;Lia Rimondini","doi":"10.1016/j.mtbio.2025.101766","DOIUrl":"10.1016/j.mtbio.2025.101766","url":null,"abstract":"<div><div>In the face of advancements in osteosarcoma research, existing preclinical models – including <em>in vitro</em> (i.e., two- and three-dimensional cell cultures, organoids) and <em>in vivo</em> approaches (i.e., xenografts, animal models) – are often characterised by low translatability, limiting their predictive power for clinical outcomes. This study investigated the potential use of a 3D-printed β-tricalcium phosphate (β-TCP) scaffold as a bone-mimicking environment in an advanced <em>in vitro</em> osteosarcoma preclinical model. The compatibility of the scaffold with osteosarcoma cell spheroids, endothelial cells, and primary bone marrow-derived mesenchymal stem cells (pBMSCs) was evaluated along with its physicochemical characteristics. Transcriptomic analysis of pBMSCs on the scaffolds revealed gene expression profiles indicating pronounced extracellular matrix organisation and minor osteogenic activity. The model effectively replicated significant aspects of the tumour microenvironment in a tri-culture system, with dynamic perfusion enhancing metabolic activity. The developed scaffold-based model was employed in the doxorubicin cytotoxicity test. The physiological significance of the tri-culture was demonstrated by its distinct doxorubicin accumulation, in contrast to spheroid monocultures. Despite the limitations of the proposed approach regarding efficient vascularisation of the model, this study highlights the potential of 3D-printed β-TCP scaffolds in tumour modelling to support physiologically relevant preclinical models.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101766"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of GDNF-Gel/HA-Mg nerve conduit and its role in repairing peripheral nerve defects","authors":"Yuanqing Cai ,&nbsp;Yi Chen ,&nbsp;Hongyan Li ,&nbsp;Yanyu Wang ,&nbsp;Guangyang Zhang ,&nbsp;Jialin Liang ,&nbsp;Leifeng Lv ,&nbsp;Ying Huang ,&nbsp;Wenming Zhang ,&nbsp;Xiaoqian Dang ,&nbsp;Xinyu Fang ,&nbsp;Yong Wang","doi":"10.1016/j.mtbio.2025.101764","DOIUrl":"10.1016/j.mtbio.2025.101764","url":null,"abstract":"<div><h3>Background</h3><div>Magnesium (Mg) and its alloys are receiving increasing attention in peripheral nerve regeneration, but they were limited due to the low corrosion resistance and rapid degradation. In this study, GDNF-Gel/HA-Mg was prepared and its value in peripheral nerve defects repairment was explored both <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>A hydroxyapatite (HA) coating was first applied to the pure Mg surface, followed by the formation of gelatin methacrylate (GelMA) loaded with glial cell-derived neurotrophic factor (GDNF) on the HA-coated Mg surface. GDNF-Gel/HA-Mg corrosion resistance was explored. The effect of GDNF-Gel/HA-Mg conduit on Schwann cell proliferation and migration abilities were investigated. And sciatic nerve defects models were established to explored the role of GDNF-Gel/HA-Mg conduit in peripheral nerve defects repairment.</div></div><div><h3>Findings</h3><div>The electrochemical, immersion, and hydrogen evolution experiments indicated that the corrosion resistance in phosphate buffer saline (PBS) of pure Mg was significantly improved by the GDNF-Gel/HA coating. Cell cycle, Cell Count Kit-8 (CCK-8), and clone formation assays indicated that GDNF-Gel/HA-Mg promoted the proliferation of Schwann cells. Scratch and Transwell assay results demonstrated that GDNF-Gel/HA-Mg promoted Schwann cell migration ability dose-dependently. GDNF-Gel/HA-Mg was found to enhance the secretion of nerve growth factor (NGF) and the expression of p75^NTR. Flow cytometry results showed that GDNF-Gel/HA-Mg could reduce H₂O₂-induced oxidative stress and Schwann cell apoptosis. GDNF-Gel/HA-Mg inhibited M1 macrophage polarization while facilitated M2 macrophage polarization in a concentration-dependent manner. The <em>in vivo</em> studies demonstrated that GDNF-Gel/HA-Mg conduit could significantly promote the regeneration and myelination of sciatic nerve, as well as the recovery of denervated gastrocnemius atrophy.</div></div><div><h3>Interpretation</h3><div>The GDNF-Gel/HA-Mg conduit prepared in this study exhibited good hydrophilicity and corrosion resistance and greatly enhanced the proliferation, migration, and invasion abilities of Schwann cells, as well as peripheral nerve regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101764"},"PeriodicalIF":8.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-responsive nanoscale ultrasound contrast agent as an oxidative stress amplifier for enhanced DNA damage in BRCA-proficient ovarian cancer","authors":"Jialu Zhang ,&nbsp;Xiaoxuan Wang ,&nbsp;Lu Guo ,&nbsp;Shan Xiao ,&nbsp;Dong Meng ,&nbsp;Mengmeng Shang ,&nbsp;Xiao Sun ,&nbsp;Dandan Shi ,&nbsp;Yading Zhao ,&nbsp;Rui Liu ,&nbsp;Shuting Huang ,&nbsp;Xinyu Zeng ,&nbsp;Jie Li","doi":"10.1016/j.mtbio.2025.101761","DOIUrl":"10.1016/j.mtbio.2025.101761","url":null,"abstract":"<div><div>PARP inhibitor (PARPi)-based synthetic lethal therapies have displayed limited benefits in BRCA-proficient ovarian cancer. To potentiate the application of PARPi, an ultrasound contrast agent OLA-NDs for delivery of the PARPi olaparib (OLA) was established for enhancing DNA damage by blocking DNA repair. OLA-NDs were endowed with endogenous pH- and exogenous ultrasound (US)-responsiveness to target tumors, as well as contrast-enhanced US imaging for diagnostic and therapeutic integration. OLA-NDs could upregulate NOX4 to induce oxidative stress and sensitize BRCA wild-type A2780 cells to DNA oxidative damage through the utilization of ultrasound-targeted microbubble destruction (UTMD). In addition, the strategy further increased ROS production by interfering with mitochondrial function, thereby exacerbating DNA double-strand breaks (DSBs) and inducing mitochondria-mediated apoptosis. As a consequence, the combined application of UTMD and OLA-NDs demonstrated significant antitumor effects <em>in vitro</em> and <em>in vivo</em>. This combined strategy of amplifying oxidative damage improved lethality by promoting DNA DSBs and apoptosis with reduced adverse side effects, which would provide new insight for the clinical application of PARPi in BRCA-proficient ovarian cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"32 ","pages":"Article 101761"},"PeriodicalIF":8.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}