Journal of Nanobiotechnology最新文献

{"title":"A ferroptosis-based intelligent nanoplatform with chemo-sonodynamic therapy carrying oxygen for improving tumor suppression and antitumor immunity.","authors":"Weilin Wang, Qiaoying Hu, Chunyan Wu, Jiayue Ding, Chuanxiu Zhu, Jiayao Wen, Yingchao Li, Menghan Yang, Yujie Wang, Deqing Sun, Guangxi Zhai, Yanan Zhang","doi":"10.1186/s12951-026-04409-y","DOIUrl":"https://doi.org/10.1186/s12951-026-04409-y","url":null,"abstract":"<p><p>Ferroptosis and sonodynamic therapy (SDT) have both been recognized as powerful weapons in cancer treatment, especially in non-small-cell lung carcinoma (NSCLC) recently. However, the lack of effective sono-sensitizer and ferroptosis regulator limited their usage. In order to overcome the limitation, a novel nanoplatform of DTX-CS/ART/PFCA@RGD (cRCAPD) was fabricated based on SDT and ferroptosis. Nanoparticles, under the action of c(RGDfk) cyclic peptides and their skeleton chondroitin sulfate (CS), could specifically target αvβ3 and CD44 receptors, respectively, thereby targeting tumor sites. Meanwhile, the peroxy-bridge structure of ART disrupted the intracellular iron homeostasis while generating highly toxic reactive oxygen species (ROS) under the SDT. Docetaxel (DTX) in nanoparticles led to the excellent apoptosis of A549 cells. Oxygen carried by PFCA alleviated the tumor hypoxic microenvironment, downregulated HIF-1α, and provided substrates for SDT. Further, the nanoparticles showed a strong immunogenic cell death (ICD) effect, modulating the number of T cells and dendritic cells in tumor-bearing mice. In summary, the proposed therapeutic strategy based on SDT and ferroptosis holds promising potential for synergistic treatment of lung cancer in future clinical applications.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic LHRH-targeted nanogels for spatiotemporal-enhanced chemo-dynamic therapy of cancer.","authors":"Jixue Wang, Jianhui Li, Min Liu, Mengxiong Sun, Yingqi Hua, Ji Lu, Yanhong Liu, Jing Xu","doi":"10.1186/s12951-026-04521-z","DOIUrl":"https://doi.org/10.1186/s12951-026-04521-z","url":null,"abstract":"<p><p>Efficient delivery of therapeutic agents to target lesions persists as a significant challenge in cancer therapy. Herein, we report a biomimetic, near-infrared (NIR)/ultrasound (US)-responsive bifunctional drug delivery system that provides spatiotemporally programmed chemo-photodynamic therapy (PDT)/sonodynamic therapy (SDT) for prostate cancer. The designed formulation comprises reduction-sensitive nanogels encapsulated within RBC membranes, surface-functionalized with LHRH for targeted delivery (termed LHRH-RBC/Ce6-NG/HCPT). Chlorin e6 (Ce6), a photosensitizer and sonosensitizer, was embedded within the RBC membrane shell, while the anticancer compound 10-hydroxycamptothecin (HCPT) was encapsulated within the nanogel core structure of poly(L-glutamic acid)-poly(L-phenylalanine-co-L-cystine) nanogels. Compared with free Ce6 and HCPT, the designed formulation markedly extended systemic retention and improved intratumoral deposition. Furthermore, tumor‑localized NIR or US stimulation induced the production of reactive oxygen species (ROS), which enhanced nanovesicle uptake by increasing tumor cell membrane fluidity and concurrently disrupted the RBC membrane, leading to the rapid, intracellular glutathione-triggered release of HCPT. The released HCPT further synergized with PDT/SDT to amplify ROS generation and exacerbate mitochondrial dysfunction, thereby enhancing tumor cell killing. The spatiotemporally coupled dynamic-chemotherapy maximized on-tumor efficacy while minimizing off-target toxicity. In vivo studies confirmed that, LHRH-RBC/Ce6-NG/HCPT achieved potent synergistic effects in both PDT/chemotherapy and SDT/chemotherapy, demonstrating its potential as an effective and safe treatment strategy for prostate cancer.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 'sugar' side of extracellular vesicle-glycome: a panorama from basic characteristics, deciphering technologies, functions, to applications.","authors":"Yufei Yan, Ying Zhu, Yifan Wang, Luru Dai, Linglong Zou, Zhigang Wang","doi":"10.1186/s12951-026-04475-2","DOIUrl":"https://doi.org/10.1186/s12951-026-04475-2","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) represent a heterogeneous group of lipid-enclosed vesicular structures. Despite their tiny bodies, EVs harbor a rich repertoire of functional molecular entities. Therein, the glycome-a diverse ensemble of glycan structures-is increasingly recognized as an essential piece of the EV biology jigsaw.</p><p><strong>Main body: </strong>This review presents a comprehensive overview of the research advances in EV glycome, recapitulating its fundamental characteristics (i.e., multiformity and heterogeneity), deciphering methodologies, biological functions, and biomedical applications. EVs are found to be enriched with diverse glycosylated components, including glycoproteins, glycolipids, proteoglycans, glycoRNAs, and free glycans. These glycome features can exhibit considerable differences across EV samples due to factors such as cellular origin, parent-cell state, EV subtype, and even isolation method. The toolkit for deciphering is undergoing substantial expansion. Besides classical glycomic methods, a series of advanced technologies has been developed to meet the specific demands of EV glycome analysis. Delving into its biological functions, EV glycome is widely involved in EV biogenesis, EV cargo sorting, EV-cell communication, immune regulation, and disease progression. It also holds immense promise across a broad range of biomedical applications, particularly in developing disease biomarkers, designing therapeutic platforms, modulating immunological activities, and advancing EV isolation methodologies.</p><p><strong>Conclusion: </strong>The past two decades have witnessed a progressive advancement in the understanding of EV glycome. Nevertheless, the field remains in its nascent phase. A multitude of unresolved issues and challenges persist, such as underexplored basic biology characteristics, limitations in analytical sensitivity and resolution due to inadequate deciphering techniques, poorly understood mechanisms underlying biological functions, and insufficiency for practical clinical implementation. This review outlines the current knowledge of EV glycome and underscores its significance in basic biology and translational applications, thereby serving as a robust foundational resource to support and accelerate future advancement.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional plasmonic nanopores for DNA-PAINT and dual-material Au/Si architectures.","authors":"German Lanzavecchia, Anastasiia Sapunova, Alan M Szalai, Shukun Weng, Ali Douaki, Makusu Tsutsui, Roman Krahne, Guillermo Acuna, Denis Garoli","doi":"10.1186/s12951-026-04509-9","DOIUrl":"https://doi.org/10.1186/s12951-026-04509-9","url":null,"abstract":"<p><p>Plasmonic nanopores combine nanofluidic confinement with electromagnetic field enhancement, enabling optical interrogation of single molecules in sub-wavelength volumes. Building on our previously developed three-dimensional dielectric nanopore platform, here we introduce 3D plasmonic nanopores as an optically active extension for single-molecule studies. We demonstrate, to our knowledge, the first implementation of DNA-PAINT within a solid-state nanopore, showing that transient hybridization events can be optically resolved within a confined plasmonic geometry. In parallel, DNA spacers of controlled length are used to position fluorophores at defined nominal distances from the metallic surface, revealing a non-monotonic fluorescence response consistent with the interplay between electromagnetic enhancement and metal-induced quenching, with an optimum around 6 nm. Finally, we introduce a novel dual-material Au/Si nanopore geometry as a hybrid plasmonic-semiconducting architecture. Static fluorescence measurements with DNA spacers and Rhodamine 6G reveal an optical response distinct from that of fully metallic Au nanopores, while simulations indicate asymmetric electromagnetic field distributions in the multi-material design. Together, these results establish 3D plasmonic nanopores as a platform for single-molecule optical techniques and show that dual-material nanopores provide an additional design parameter for modifying nanoscale optical response.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic hybrid nanoparticles for dual regulation of macrophage pyroptosis and metabolism in rheumatoid arthritis.","authors":"Guang Yang, Lingxiao Xu, Ruijie Zhang, Zhenyu Zhu, Kelei Wang, Kaipeng Jin, Yifan Wu, Hanxu Huang, Jiaxuan Zou, Wushi Cui, Xiaohua Yu, Lingling Sun, Zhenxuan Shao","doi":"10.1186/s12951-026-04502-2","DOIUrl":"https://doi.org/10.1186/s12951-026-04502-2","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA), a chronic and debilitating autoimmune inflammatory disease, is critically driven by macrophages within the inflamed synovium. The inflammatory cascade is sustained by a synergistic imbalance between macrophage pyroptosis and metabolic dysfunction, resulting in the formation of a dual barrier to effective intervention. GSDME-targeted siRNA delivery effectively blocks pyroptosis; however, uncorrected metabolic defects leave \"saved\" macrophages in a proinflammatory state, thereby aggravating RA. To address this \"dual dilemma\", folic acid-modified macrophage membrane-lipid hybrid nanoparticles (FA-MMLNPs) were engineered for spatiotemporally coordinated codelivery of GSDME siRNA (siG) and 4-octyl itaconate (4-OI). The biomimetic membrane promotes inflammatory homing, folic acid enhances FR-positive macrophage endocytosis, and the lipid core protects the siRNA and ensures synchronous release. Mechanistically, SiG inhibits pyroptosis, whereas 4-OI restores mitochondrial metabolism to reprogram macrophages to an anti-inflammatory phenotype. This integrated material platform organically combines pathway-specific gene silencing, metabolic correction, and precise biointerface engineering, providing a versatile paradigm for material design in RA and other inflammation-driven diseases.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic phycocyanin lipid-based nanoparticles ameliorate placental dysfunction and restore angiogenic balance in a pre-eclampsia model.","authors":"Hongxia Yuan, Jian He, Jiahua Niu, Min Zhou","doi":"10.1186/s12951-026-04498-9","DOIUrl":"https://doi.org/10.1186/s12951-026-04498-9","url":null,"abstract":"<p><p>Pre-eclampsia (PE) is a life-threatening pregnancy disorder associated with substantial maternal and fetal morbidity and mortality worldwide. Despite its clinical significance, current treatment strategies remain largely limited to symptomatic management, underscoring the urgent need for targeted interventions that address underlying pathophysiology. Lipid-based nanoparticles (LBNPs) have emerged as promising platforms for placental drug delivery. However, achieving precise and efficient site-specific accumulation remains a major challenge. Herein, we developed trophoblast cell membrane-hybridized, phycocyanin (PC)-loaded lipid-based nanoparticles (LBNP-PC@M) to enhance placental targeting. By integrating the intrinsic bioactivity of phycocyanin with the biomimetic targeting capability of trophoblast membranes, LBNP-PC@M facilitates preferential accumulation in the placenta and subsequent localized release of the therapeutic cargo, thereby improving angiogenic balance and metabolic homeostasis. In an inflammation-induced PE model, LBNP-PC@M treatment enhances placental vascularization, mitigates fetal growth restriction, and alleviates key pathological features associated with PE. Multi-omics analyses, including transcriptomics and metabolomics, indicate that LBNP-PC@M modulates pathways related to angiogenesis, oxidative stress responses, and amino acid metabolism, while partially restoring dysregulated histamine metabolism in PE placentas. Collectively, this study presents a biomimetic nanoplatform for placenta-targeted delivery of bioactive compounds, offering a promising strategy for modulating placental dysfunction and advancing therapeutic approaches for PE and related placental disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-targeted liposomal RNAi therapy suppresses breast cancer and modulates tumor microenvironment.","authors":"Sujeong Lee, Seung Hee Choi, Hui Bang Cho, Chae Won Cho, Jungsun Lee, Gyuwon So, Hye Jin Kim, Kyung-Soon Park, Keun-Hong Park","doi":"10.1186/s12951-026-04450-x","DOIUrl":"https://doi.org/10.1186/s12951-026-04450-x","url":null,"abstract":"<p><p>Liposomes are widely used nanocarriers, but their clinical translation remains limited by poor tumor selectivity and inefficient nucleic acid delivery. To address these challenges, we designed multifunctional liposomes incorporating phenylboronic acid (PBA) for tumor targeting, ginsenoside Rh2 (Rh2) as both a cholesterol-mimetic stabilizer and intrinsic anticancer agent, and small interfering RNA against vascular endothelial growth factor (VEGF). VEGF was selected for its pivotal role in tumor angiogenesis and to counteract the paradoxical pro-angiogenic effect of Rh2. PBA-modified liposomes exhibited enhanced tumor accumulation and cellular uptake compared with non-targeted controls. Rh2 induced direct cytotoxicity, while VEGF silencing further suppressed angiogenesis together producing synergistic antitumor activity. In vivo, Rh2-PBA-siVEGF liposomes (RhPLIPO-siVEGF) and Rh2-PBA-Negative Control siRNA (siNC) liposomes (RhPLIPO-siNC) were evaluated in a 4T1 orthotopic breast tumor model. Both formulations elicited effects characterized by increased infiltration of T cells and M1 macrophages. Notably, RhPLIPO-siVEGF treatment significantly reduced tumor growth and microvascular density compared with RhPLIPO-siNC, confirming synergy between Rh2-mediated cytotoxicity and VEGF knockdown. Overall, this multifunctional liposomal system integrates tumor targeting, intrinsic cytotoxicity, and RNA interference-mediated anti-angiogenesis with minimal adverse effects, offering a potent and versatile nanoplatform for targeted breast cancer therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo toxicity assessment of silica-coated iron oxide nanoparticles for nanowarming in organ cryopreservation.","authors":"Onyinyechukwu Justina Oziri, Cameron Scheithauer, Henry L Wong, Michael L Etheridge, Erik B Finger, John C Bischof","doi":"10.1186/s12951-026-04471-6","DOIUrl":"https://doi.org/10.1186/s12951-026-04471-6","url":null,"abstract":"<p><p>The ability to cryopreserve and rewarm whole organs without damage has the potential to transform transplantation by enabling long-term banking and global organ sharing. Successful transplantation of rat kidneys cryopreserved and rewarmed using nanowarming, a technique in which silica coated iron oxide nanoparticles (sIONP) are perfused throughout the organ's vasculature along with cryoprotective agents (CPAs), which are then both washed out of the organ after rewarming prior to transplant has recently been reported. To support development towards clinical organ scale translation, the potential toxicity of sIONP in male Sprague-Dawley rats was evaluated, administering doses six to seven orders of magnitude higher than the estimated systemic exposure corresponding to the highest reported residual iron levels in organs following nanowarming and cryopreservation (3.36 ng Fe/kg). These doses are effectively within the range of a theoretical worst-case scenario, where a fully loaded kidney is transplanted (10.5-14 mg Fe/kg) without washout. Toxicity was assessed at 24 h for (5, 12, and 20 mg Fe/kg) and over 28 days for 12 mg Fe/kg dose. Furthermore, plasma pharmacokinetics, hematology, clinical chemistry, biodistribution and histopathology were evaluated. No overt toxicity was observed at the lower doses, while some adverse effects emerged at the highest dose of 20 mg Fe/kg. These findings suggest minimal toxicity associated with sIONP injections of a dose equivalent to a fully loaded organ, supporting the translational potential of sIONP for organ nanowarming.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed dictamni-calcium silicate scaffolds modulate the osteoimmune microenvironment and enhance macrophage-derived exosomal miR-21 signaling in vascularized bone regeneration.","authors":"Chia-Che Ho, Tuan-Ti Hsu, Yen-Hong Lin, Ting-You Kuo, Cheng-Yu Chen, Shang-Hsiu Hu, Jen-Ting Huang, Tsung-Li Lin, Der-Yang Cho, Ming-You Shie","doi":"10.1186/s12951-026-04507-x","DOIUrl":"https://doi.org/10.1186/s12951-026-04507-x","url":null,"abstract":"<p><p>Reconstruction of critical-sized bone defects remains a formidable clinical challenge due to a persistent, localized, pro-inflammatory microenvironment that disrupts the coordinated process of osteogenic-angiogenic coupling. To address this, we engineered 3D-printed calcium silicate scaffolds containing Dictamni Radicis Cortex to modulate the osteoimmune niche. In vitro models demonstrated that Dic5 scaffolds effectively attenuated the pro-inflammatory state, promoting the transition of macrophages from an M1 to a proregenerative M2 phenotype, characterized by anti-inflammatory cytokine secretion. In parallel, elevated levels of angiogenesis-related factors were also observed. In vivo assessments using a rabbit bone defect model corroborated these findings, with Dic5 scaffolds implantation was associated with the rapid resolution of local tissue inflammation, facilitation of early vascular network formation, and accelerated highly mineralized bone healing compared to the Dic0 group. To elucidate the molecular mechanisms linking this immunomodulation to the observed therapeutic efficacy, we investigated macrophage-mediated paracrine signaling. Transcriptomic profiling using next-generation sequencing revealed that extracellular vesicles secreted by these modulated macrophages were significantly enriched with miR-21-5p. Subsequent in vitro mechanistic studies demonstrated that upon internalization by human mesenchymal stem cells, exosomal miR-21 acts as an epigenetic regulator, targeting and silencing inhibitory genes, specifically Spry1 and Pten, thereby unlocking downstream signaling pathways to promote the expression of osteogenic effectors, including Runx2 and osteocalcin. Finally, blocking miR-21 with a specific inhibitor significantly abolished Dic5-M2EV-mediated osteogenic capabilities. In summary, this study presents a translatable phytochemically engineered 3D bioscaffold and elucidates the regulatory role of the biomaterial-macrophage-exosomal miR-21 axis, providing a promising cell-free therapeutic strategy for vascularized bone tissue engineering.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4D printed hydrogel scaffolds with shape morphing by near-infrared to promote bone regeneration through immune and vascular coupling.","authors":"Chuqiao Wei, Jingjie Zhai, Yidi Zhang, Yuemeng Zhu, Yuzhu Han, Yangyang Li, Sicong Ren, Quan Lin, Hanchi Wang, Yanmin Zhou","doi":"10.1186/s12951-026-04386-2","DOIUrl":"https://doi.org/10.1186/s12951-026-04386-2","url":null,"abstract":"<p><p>The regeneration of critical-size irregular bone defects, especially those with irregular shapes, remains clinically challenging due to inadequate shape-conformability, immune dysregulation, poor vascularization and the unsatisfied osteogenic bioactivity. Self-fitting tissue scaffolds that can be implanted by minimally invasive procedures are a promising solution. Herein, we present a 4D-printed hydrogel scaffold (PASN) composed of polydopamine (PDA), alginate (Alg), and strontium ions (Sr²⁺), that is 3D-printed and NIR-induced shape-morphing to match defect and orchestrate both immunomodulation and osteogenesis. Compared with traditional hydrogels, this PASN scaffold enables shape morphing with quantitatively tunable curvature and controllable deformation speed responsible to NIR light, while functionally fitting irregular bone defects. By eliminating reactive oxygen species and driving M2 macrophage polarization through PDA, PASN improves immune regulation through the PI3K signaling pathway as well as stimulates osteogenesis and angiogenesis through release of Sr²⁺. The deformation angle of the scaffold is adjusted by the laser power, irradiation time, and the designed pattern of alginate PDA struts, whereas the temperature gradient formed between the upper and lower layers under NIR irradiation induces bending toward the light source. Dome-shaped calvarial defects, maxillary sinus floor lift and horizontal bone augmentation surgeries demonstrate the PASN scaffold markedly enhances bone regeneration. Collectively, the personalised and bioactive scaffold with NIR-responsive shape-morphing may be a promising biomaterial for clinical-size and irregular bone defect regeneration.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}