Journal of Nanobiotechnology最新文献

{"title":"Injectable hydrogels with ROS-triggered drug release enable the co-delivery of antibacterial agent and anti-inflammatory nanoparticle for periodontitis treatment.","authors":"Yujing Zhu, Ziliang Xiu, Xiaoxi Jiang, Huifang Zhang, Xiaofeng Li, Yunru Feng, Bojiang Li, Rui Cai, Chunhui Li, Gang Tao","doi":"10.1186/s12951-025-03275-4","DOIUrl":"10.1186/s12951-025-03275-4","url":null,"abstract":"<p><p>Periodontitis, a chronic inflammatory disease caused by bacteria, is characterized by localized reactive oxygen species (ROS) accumulation, leading to an inflammatory response, which in turn leads to the destruction of periodontal supporting tissues. Therefore, antibacterial, scavenging ROS, reducing the inflammatory response, regulating periodontal microenvironment, and alleviating alveolar bone resorption are effective methods to treat periodontitis. In this study, we developed a ROS-responsive injectable hydrogel by modifying hyaluronic acid with 3-amino phenylboronic acid (PBA) and reacting it with poly(vinyl alcohol) (PVA) to form a borate bond. In addition, the ROS-responsive hydrogel encapsulated the antibacterial agent minocycline hydrochloride (MH) and Fe-Quercetin anti-inflammatory nanoparticles (Fe-Que NPs) for on-demand drug release in response to the periodontitis microenvironment. This hydrogel (HP-PVA@MH/Fe-Que) exhibited highly effective antibacterial properties. Moreover, by modulating the Nrf2/NF-κB pathway, it effectively eliminated ROS and promoted macrophage polarization to the M2 phenotype, reducing inflammation and enhancing the osteogenic differentiation potential of human periodontal ligament stem cells (hPDLSCs) in the periodontal microenvironment. Animal studies showed that HP-PVA@MH/Fe-Que significantly reduced alveolar bone loss and enhanced osteogenic factor expression by killing bacteria and inhibiting inflammation. Thus, HP-PVA@MH/Fe-Que hydrogel had efficient antibacterial, ROS-scavenging, anti-inflammatory, and alveolar bone resorption-alleviation abilities, showing excellent application potential for periodontitis healing.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"205"},"PeriodicalIF":10.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of immune microenvironments by polyetheretherketone surface topography for improving osseointegration.","authors":"Yuqing Zhao, Yanxin An, Fan Wu, Lipeng Liu, Franklin R Tay, Yang Jiao, Jing Wang","doi":"10.1186/s12951-025-03272-7","DOIUrl":"10.1186/s12951-025-03272-7","url":null,"abstract":"<p><p>Optimizing the immune microenvironment is essential for successful implant osseointegration. In this study, four different nano/microstructures were fabricated on polyetheretherketone (PEEK) substrates by varying the agitation speed during sulfonation to influence osteoimmunomodulation and implant integration. The results indicate that nano/microstructures with minimal dimensions (SP450) inhibit actin polymerization by reducing calcium influx through PIEZO1, activating the anti-inflammatory M2 macrophage phenotype. Among the tested specimens, SP450 exhibited the lowest expression levels of tumor necrosis factor-α and interleukin-1β while releasing the highest levels of anti-inflammatory factors, including interleukin-4 and interleukin-10. This optimized immune environment promotes the osteogenesis of MC3T3-E1 pre-osteoblasts and enhances the osseointegration of PEEK implants. Transcriptomic analysis and validation experiment further revealed that SP450 inhibits osteoclastic differentiation by down-regulating transforming growth factor-β2 and suppressing the NF-κB signaling pathway. These findings suggest that manipulating the surface topography of PEEK implants is an effective strategy for enhancing osseointegration with promising clinical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"199"},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MXene-based nanosheet for enhanced glioma therapy via photonic hyperthermia to boost the abscopal effect of radioimmunotherapy.","authors":"Huan Zhu, Zhaoyuan Zhang, Rong Jiang, Liangfu Xu, Xiangdi Yang, Jie Chen, Zhenning Wang, Xiao Xu, Zhigang Liu","doi":"10.1186/s12951-025-03288-z","DOIUrl":"10.1186/s12951-025-03288-z","url":null,"abstract":"<p><p>Radiotherapy (RT) effectiveness is limited by low DNA damage in tumor cells, surrounding tissue harm, and tumor radioresistance with active DNA repair. Herein, we have engineered a two-dimensional nanomaterial consisting of MXene nanosheets at its core, coated with gold nanorods and a cisplatin shell, and further modified with polyvinyl alcohol, referred to as APMP. The APMP exploits its distinctive electronic properties and photothermal effects to augment radiosensitivity and impede DNA damage repair mechanisms. In vitro experiments demonstrate that APMP elevates reactive oxygen species (ROS) production to approximately 2.6 times higher than that achieved with radiotherapy alone, thereby significantly enhancing the sensitivity to radiotherapy. Combining APMP with photothermal therapy (PTT) and RT is a promising glioblastoma treatment strategy, achieving tumor destruction via localized hyperthermia and overcoming radioresistance. This approach achieves precise tumor targeting, reducing side effects and enhancing therapeutic response in preclinical models. The novel core-shell design enables potent radiotherapy-specific radiosensitizers that drive immunogenic cell death, enhancing glioblastoma combination immunotherapy. This universal strategy heralds a new era in integrating radiotherapy sensitizers with immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"203"},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted nanovesicles for ursodeoxycholic acid delivery to combat neurodegeneration by ameliorating mitochondrial dysfunction.","authors":"Shizheng Zhang, Mengmeng Li, Yuan Li, Shike Yang, Jian Wang, Xiaoxiang Ren, Xiuhui Wang, Long Bai, Jianping Huang, Zhen Geng, Guosheng Han, Yibin Fang, Jiacan Su","doi":"10.1186/s12951-025-03258-5","DOIUrl":"10.1186/s12951-025-03258-5","url":null,"abstract":"<p><p>Mitochondria are pivotal in sustaining oxidative balance and metabolic activity within neurons. It is well-established that mitochondrial dysfunction constitutes a fundamental pathogenic mechanism in neurodegeneration, especially in the context of Parkinson's disease (PD), this represents a promising target for therapeutic intervention. Ursodeoxycholic acid (UDCA), a clinical drug used for liver disease, possesses antioxidant and mitochondrial repair properties. Recently, it has gained attention as a potential therapeutic option for treating various neurodegenerative diseases. However, multiple barriers, including the blood-brain barrier (BBB) and cellular/mitochondrial membranes, significantly hinder the efficient delivery of therapeutic agents to the damaged neuronal mitochondria. Macrophage-derived nanovesicles (NVs), which can traverse the BBB in response to brain inflammation signals, have demonstrated promising tools for brain drug delivery. Nevertheless, natural nanovesicles inherently lack the ability to specifically target mitochondria. Herein, artificial NVs are loaded with UDCA and then functionalized with triphenylphosphonium (TPP) molecules, denoted as UDCA-NVs-TPP. These nanovesicles specifically accumulate in damaged neuronal mitochondria, reduce oxidative stress, and enhance ATP production by 42.62%, thereby alleviating neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP+). Furthermore, UDCA-loaded NVs modified with TPP successfully cross the BBB and accumulate in the striatum of PD mice. These nanoparticles significantly improve PD symptoms, as demonstrated by a 48.56% reduction in pole climb time, a 59.09% increase in hanging ability, and the restoration of tyrosine hydroxylase levels to normal, achieving remarkable therapeutic efficacy. Our work highlights the immense potential of these potent UDCA-loaded, mitochondria-targeting nanovesicles for efficient treatment of PD and other central neurodegenerative diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"202"},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young fibroblast-derived migrasomes alleviate keratinocyte senescence and enhance wound healing in aged skin.","authors":"Hanlin Tu, Yingliang Shi, Yi Guo, Zhongyang Zou, Yuyan He, Jing Zhou, Sangang He, Guoliang Sa","doi":"10.1186/s12951-025-03293-2","DOIUrl":"10.1186/s12951-025-03293-2","url":null,"abstract":"<p><strong>Background: </strong>Alterations in intercellular communication driven by cellular senescence constitute an important factor in skin aging. Migrasome, a newly discovered vesicular organelle, efficiently participates in intercellular communication; however, the relationship between cellular senescence and migrasomes remains unreported.</p><p><strong>Objective: </strong>This study aims to explore the possible relationship between cellular senescence and migrasomes formation, and investigate the effects of young fibroblast-derived migrasomes on senescent keratinocytes and wound healing in aged skin.</p><p><strong>Result: </strong>Single-cell RNA sequencing (scRNA-seq) data analysis revealed that fibroblasts exhibited the highest level of transcriptional variability during skin aging, and the degree of fibroblast senescence negatively correlated with the expression level of migrasome-associated markers. Further multiplex Immunohistochemistry (mIHC) results suggested that younger mouse skin contained more migrasomes than older mouse skin. Transmission electron microscopy (TEM) observations demonstrated abundant migrasomes in the skin from young individuals. In vitro experiments indicated that young fibroblasts produced significantly more migrasomes than senescent fibroblasts, as confirmed by wheat germ agglutinin (WGA) staining and scanning electron microscopy (SEM). Importantly, purified migrasomes from young fibroblasts were found to reduce the expression of senescence-associated markers in HaCaT cells. In vivo, using a wound healing model in naturally aged mice, we observed that migrasomes derived from young fibroblasts not only accelerated wound healing but also reduced senescence-associated marker expression in the skin.</p><p><strong>Conclusion: </strong>Migrasomes formation ability reduced during skin aging progress, and young fibroblast-derived migrasomes rejuvenated senescent keratinocytes and promoted wound healing in aged skin. These findings offer new ideas for alleviating skin aging and enhancing wound healing in aged skin.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"200"},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell-derived extracellular vesicles alleviate autism by regulating microglial glucose metabolism reprogramming and neuroinflammation through PD-1/PD-L1 interaction.","authors":"Qian Qin, Linlin Fan, Xin Zeng, Danyang Zheng, Han Wang, Mengyue Li, Yutong Jiang, Hui Wang, Hao Liu, Shengjun Liang, Lijie Wu, Shuang Liang","doi":"10.1186/s12951-025-03250-z","DOIUrl":"10.1186/s12951-025-03250-z","url":null,"abstract":"<p><p>Neuroinflammation triggered by microglia activation is hallmark of autism spectrum disorder (ASD), and this process includes crucial metabolic reprogramming from oxidative phosphorylation to glycolysis, which may cause neuron loss and functional impairment. The inhibitory immune checkpoint programmed cell death protein 1 (PD-1) on immune cells is an important target for tumor immunotherapy. However, the immunomodulatory effects of PD-1 in ASD remains to be elusive. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exhibit immunomodulatory capabilities in a range of neurological diseases. Our findings indicated the expression of PD-L1 on MSC-EVs, potentially facilitating signaling to PD-1-expressing microglia. Here, we showed how MSC-EVs activated of PD-L1/PD-1 axis and ameliorated glycolysis, neuroinflammation and autism-like behaviors. After first detecting elevated glycolysis and neuroinflammation in prefrontal cortex (PFC) tissue from the maternal immune activation (MIA) mice, we also demonstrated that PD-1 expression level was upregulated in microglia. Following given MSC-EVs carried PD-L1 into adult MIA offspring mice via intranasal administration, which bound with PD-1 on microglia and then the autism-like behaviors were alleviated as well. Further experiments verified that MSC-EVs could decreased the level of glycolysis and neuroinflammation by PD-1/ERK/HIF-1α pathway in the primary microglia in PFC of MIA offspring mice. Pharmacological blockade and genetic inhibition of PD-1 could weaken the effect of MSC-EVs and aggravate microglial dysfunction, glycolysis and autism-like behaviors in MIA offspring mice. Futhermore, PD-L1 deficient weakened the effect of MSC-EVs on neuroinflammation, glycolysis and autism-like behaviors in MIA offspring mice. Our research indicated the significant immunomodulatory capabilities of MSC-EVs, which play an important role in reprogramming microglial glucose metabolism and suppressing neuroinflammation in ASD. By activating the PD-L1/PD-1 axis and inhibiting the downstream ERK/HIF-1α pathway, MSC-EVs were found to alleviate autism-like behaviors, which revealing a novel pathological mechanism and offering promising therapeutic insights into ASD.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"201"},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginseng exosomes modulate M1/M2 polarisation by activating autophagy and target IKK/IкB/NF-кB to alleviate inflammatory bowel disease.","authors":"Song Yang, Liangliang Fan, Lijia Yin, Yueming Zhao, Wenjing Li, Ronghua Zhao, Xuxia Jia, Fusong Dong, Ze Zheng, Daqing Zhao, Jiawen Wang","doi":"10.1186/s12951-025-03292-3","DOIUrl":"10.1186/s12951-025-03292-3","url":null,"abstract":"<p><strong>Background: </strong>Exosomes are involved in intercellular communication and regulation of the inflammatory microenvironment. In a previous study, we demonstrated that fresh ginseng exosomes (GEs) alleviated inflammatory bowel disease. However, the precise mechanism by which GEs activate the immune system and subsequently inhibit the formation of intestinal inflammatory microenvironment remains unknown.</p><p><strong>Methods: </strong>Herein, we investigated the effects of GEs on autophagy, macrophage polarisation, intestinal inflammation, and the epithelial barrier by means of transcriptome sequencing, network pharmacology, transmission electron microscopy, immunoblotting, flow cytometry and small molecule inhibitors.</p><p><strong>Results: </strong>GEs significantly activated autophagy and M2-like macrophage polarisation, which could be blocked by the autophagy inhibitor 3-methyladenine. In the co-culture system of macrophages and intestinal epithelial cells, macrophages treated with GEs secreted more interleukin-10 (IL-10) and significantly reduced Nitric oxide (NO) levels in intestinal epithelial cells in vitro. Furthermore, GEs acted directly on intestinal epithelial cells through the IKK/IкB/NF-кB signalling pathway to reduce inflammation and restore the intestinal barrier. Orally administered GEs could restore disrupted colonic barriers, alleviate inflammatory bowel responses, and regulate the polarisation of intestinal macrophages in vivo.</p><p><strong>Conclusion: </strong>In summary, GEs may be a potential treatment for inflammatory bowel disease, and targeting autophagy and macrophage polarisation may help alleviate intestinal inflammation.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"198"},"PeriodicalIF":10.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-delivery of axitinib and PD-L1 siRNA for the synergism of vascular normalization and immune checkpoint inhibition to boost anticancer immunity.","authors":"Yanhong Liu, Liming Gong, Jing Feng, Congcong Xiao, Chenfei Liu, Bohan Chen, Liqing Chen, Mingji Jin, Youyan Guan, Zhonggao Gao, Wei Huang","doi":"10.1186/s12951-025-03170-y","DOIUrl":"10.1186/s12951-025-03170-y","url":null,"abstract":"<p><p>Immune checkpoint inhibition (ICI) has become the mainstay of immunotherapy for the treatment of renal cell carcinoma (RCC). However, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy and the key reason is that RCC belongs to a vascular-rich tumor for promoting immunosuppression. Specifically, the dysfunctional tumor vasculature hinders effector T cell infiltration and induces immunosuppressive tumor microenvironment via the release of cytokine, which attenuates the therapeutic efficacy of ICI. Therefore, regulating abnormal tumor vasculature may be a promising strategy to overcome the immunosuppressive microenvironment and enhance ICI therapy. Here, we propose an NGR peptide-modified actively targeted liposome (Axi/siRNA^PD-L1@NGR-Lipo) to encapsulate the anti-angiogenic agents Axitinib and PD-L1 siRNA to promote tumor vasculature normalization and relieve immune evasion for enhanced anti-tumor immunotherapy. With NGR-mediated tumor homing and active targeting, Axi/siRNA^PD-L1@NGR-Lipo could act on tumor vascular endothelial cells to inhibit neo-angiogenesis, increase pericyte coverage and vascular perfusion, and normalize the structure and function of tumor blood vessels. Meanwhile, it also enhanced immune effector T cells and NK cells infiltration and reduced the proportion of immunosuppressive T cells including MDSC cells and Tregs, thus improving the tumor immunosuppressive microenvironment. Moreover, Axi/siRNA^PD-L1@NGR-Lipo reduced the expression of PD-L1 protein in tumor cells, restored the recognition and killing ability of cytotoxic T cells, and relieved immune evasion. As expected, Axi/siRNA^PD-L1@NGR-Lipo displayed superior anti-tumor and anti-metastatic efficacy in mice bearing RCC. Overall, this study demonstrated the important potential of regulating abnormal tumor vasculature to reshape the immunosuppressive microenvironment and boost ICI therapy, which represents a promising avenue for the synergistic anti-tumor with cancer immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"194"},"PeriodicalIF":10.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet hitchhiking vascular-disrupting agents for self-amplified tumor-targeting therapy.","authors":"Hongyu Chu, Yajun Xu, Yuezhan Shan, Mengmeng Sun, Weidong Zhao, Xuedong Fang, Na Shen, Zhaohui Tang","doi":"10.1186/s12951-025-03262-9","DOIUrl":"10.1186/s12951-025-03262-9","url":null,"abstract":"<p><p>The vascular-disrupting agent DMXAA (5,6-dimethylxanthone-4-acetic acid) exhibits potent anticancer activity by targeting tumor vasculature and activating immune responses via the cGAS-STING pathway. However, its clinical application is hindered by nonspecific targeting and significant cardiovascular toxicity. This study introduces a novel self-amplified tumor-targeting delivery system(P@NPPD)comprising azide-functionalized poly(ethylene glycol)-b-poly-[(N-2-hydroxyethyl)-aspartamide]-DMXAA (N₃-PEG-b-PHEA-DMXAA, NPPD) conjugated to DBCO modified platelets. Among them, NPPD was synthesized by conjugating DMXAA to N₃-PEG-b-poly-[(N-2-hydroxyethyl)-aspartamide] through esterification. This system enhances tumor-specific drug delivery while minimizing systemic toxicity. Leveraging the natural tumor-homing properties of platelets and the coagulation cascade, P@NPPD selectively targets exposed collagen at tumor sites, initiating a self-amplifying release of DMXAA. This approach achieved a 2.61-fold improvement in targeting efficiency and an 89.1% tumor suppression rate. In addition to improving drug accumulation at tumor sites, P@NPPD significantly activated local immune responses, enhancing therapeutic efficacy and safety. These findings underscore the potential of P@NPPD as a promising platform for cancer therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"197"},"PeriodicalIF":10.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bivalent spike-targeting nanobody with anti-sarbecovirus activity.","authors":"Iris C Swart, Oliver J Debski-Antoniak, Aneta Zegar, Thijs de Bouter, Marianthi Chatziandreou, Max van den Berg, Ieva Drulyte, Krzysztof Pyrć, Cornelis A M de Haan, Daniel L Hurdiss, Berend-Jan Bosch, Sabrina Oliveira","doi":"10.1186/s12951-025-03243-y","DOIUrl":"10.1186/s12951-025-03243-y","url":null,"abstract":"<p><p>The continued emergence and zoonotic threat posed by coronaviruses highlight the urgent need for effective antiviral strategies with broad reactivity to counter new emerging strains. Nanobodies (or single-domain antibodies) are promising alternatives to traditional monoclonal antibodies, due to their small size, cost-effectiveness and ease of bioengineering. Here, we describe 7F, a llama-derived nanobody, targeting the spike receptor binding domain of sarbecoviruses and SARS-like coronaviruses. 7F demonstrates potent neutralization against SARS-CoV-2 and cross-neutralizing activity against SARS-CoV and SARS-like CoV WIV16 pseudoviruses. Structural analysis reveals 7F's ability to induce the formation of spike trimer dimers by engaging with two SARS-CoV-2 spike RBDs, targeting the highly conserved class IV region, though concentration dependent. Bivalent 7F constructs substantially enhance neutralization potency and breadth, up to more recent SARS-CoV-2 variants of concern. Furthermore, we demonstrate the therapeutic potential of bivalent 7F against SARS-CoV-2 in the fully differentiated 3D tissue cultures mirroring the epithelium of the human airway ex vivo. The broad sarbecovirus activity and distinctive structural features of bivalent 7F underscore its potential as promising antiviral against emerging and evolving sarbecoviruses.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"196"},"PeriodicalIF":10.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}