Acta Biomaterialia最新文献

{"title":"A pH-responsive polycarbonate nanoplatform enables sequential drug release for enhanced apoptotic cascade synergy in non-small cell lung cancer therapy","authors":"Jinghang Li , Hao Liao , Shuangyu Tian , Longhui Liu , Haixing Xu , Lesan Yan","doi":"10.1016/j.actbio.2025.09.001","DOIUrl":"10.1016/j.actbio.2025.09.001","url":null,"abstract":"<div><div>Tumor heterogeneity poses formidable challenges to effective cancer therapy, necessitating the implementation of combination regimens to achieve enhanced antitumor efficacy. Optimizing drug administration sequences is pivotal to harnessing synergistic effects and achieving superadditive therapeutic outcomes (1 + 1 > 2). Erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, dynamically reprograms apoptotic pathways, sensitizing tumor cells to subsequent DNA-damaging agents like doxorubicin within a defined temporal window, thereby augmenting chemotherapy efficacy. To advance this strategy toward clinical relevance, we developed a pH-responsive nanoplatform (PEDHNPs) for sequential control of drug delivery. This system integrates a dual acid-responsive polymeric architecture comprising a hydrazone-linked polycarbonate conjugated with doxorubicin as a prodrug and a ketal-based polycarbonate enabling temporal regulation of drug release. Erlotinib is encapsulated within the hydrophobic core during micelle self-assembly. In the acidic tumor microenvironment, PEDHNPs rapidly liberate erlotinib via ketal hydrolysis, followed by sustained doxorubicin release through hydrazone cleavage. This orchestrated delivery enhances EGFR inhibition and activates caspase-8-mediated apoptosis, potentiating doxorubicin’s antitumor effect. <em>In vitro</em> experiments showed that at a doxorubicin concentration of 80 µg/mL, PEDHNPs achieved a proliferation inhibition rate of 71.54 ± 0.42 % in A549 cells, which was significantly higher than that of the monotherapy groups (Erlotinib: 31.48 ± 0.19 %; Doxorubicin: 63.18 ± 1.04 %) and the control group with amide bond conjugation (54.21 ± 1.13 %). In the NSCLC mouse model, treatment with PEDHNPs resulted in a 95.1 % reduction in tumor volume compared to the control PBS group<em>.</em> These offer a promising paradigm for achieving precise cancer therapy through sequential drug delivery.</div></div><div><h3>Statement of significance</h3><div>Tumor heterogeneity compromises the efficacy of monotherapies, necessitating rationally designed combination regimens. Optimizing drug administration sequences is critical for harnessing synergistic interactions and achieving superadditive therapeutic outcomes (1 + 1 > 2). Here, a pH-responsive polycarbonate-based nanoparticle (PEDHNP) incorporating hydrazone and ketal linkages was designed for sequential co-delivery of erlotinib and doxorubicin. This sequence-controlled release strategy achieves early EGFR inhibition followed by activation of caspase-8–mediated apoptosis, thereby potentiating the antitumor activity of doxorubicin. <em>In vitro</em>, PEDHNPs exhibited superior antiproliferative and proapoptotic effects compared with monotherapies, single-drug nanoparticles, and amide-linked nanoparticle controls. <em>In vivo</em>, PEDHNPs achieved marked tumor growth suppression in a non-small cell lung cancer model, establishing a versatile platform for precisio","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 550-567"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002154","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":"Co-assembled polypeptides-adsorbing bridge molecules to enhance macrophage efferocytosis for the resolution of periodontitis inflammation","authors":"Bang Li,&nbsp;Feng Liang,&nbsp;Ziyang Gao,&nbsp;Xianqing Zhou,&nbsp;Dujuan Zheng,&nbsp;Xinjing Zhang,&nbsp;Mengyao Sun,&nbsp;Xu Yan,&nbsp;Wanjia Li,&nbsp;Yuansong Wang,&nbsp;Xiaoxuan Lu,&nbsp;Leping Wu,&nbsp;Xiaoyu Sun,&nbsp;Hengguo Zhang,&nbsp;Jianguang Xu,&nbsp;Qingqing Wang","doi":"10.1016/j.actbio.2025.08.011","DOIUrl":"10.1016/j.actbio.2025.08.011","url":null,"abstract":"<div><div>Effective removal of apoptotic cells, namely efferocytosis, promotes inflammation resolution of periodontitis and tissue restoration. However, effective treatments to enhance macrophage efferocytosis in periodontitis are still lacking. Co-assembly of distinct building blocks is considered a versatile and effective method of modulating the structure and functionality of supramolecular materials. Herein, a biologically inert amphiphile peptide (PA) (C₁₆H₃₁O<img>NNCCCCS, PAS) was designed based on a previous amphiphile peptide (C₁₆H₃₁O<img>NNCCCCRRES(p), PARRES). We described those two peptides' co-assembly in modulating macrophage efferocytosis for periodontitis resolution. The results showed that individual PAS and PARRES co-assemble together and transform the secondary structure from α-helix to β-sheet pattern <em>via</em> hydrogen bonding. Compared with individual PAs, the composite PA adsorbed more “bridging molecules” that enhance apoptotic signal binding on macrophages. The enriched “bridging molecules” could bind to macrophages on one side <em>via</em> phagocytic receptors and attract the apoptotic cells on the other side, thus promoting efferocytosis. When injected into mice with periodontitis, composite PA promotes inflammation resolution and further promotes periodontal tissue regeneration. This study provided an easily adjustable supermolecular system that enhances efferocytosis for periodontitis and revealed insights into the relationship between physicochemical properties and biological effects of supermolecular materials.</div></div><div><h3>Statement of significance</h3><div>Efferocytosis promotes periodontitis resolution and further tissue restoration. Nevertheless, high-performance therapeutics for promoting efferocytosis are still lacking. Peptides have desirable features, including biocompatibility and sequence-specific secondary structures. A biologically amphiphile peptide (PA) was designed with a similar structure to a previous PA. We described those PAs' co-assembly in modulating efferocytosis for periodontitis resolution. Specifically, those PAs co-assemble together and transform secondary structure from α-helix to β-sheet pattern. The composite PA adsorbs more “bridging molecules,” enhancing apoptotic signals binding to macrophages and attracting apoptotic cells for promoting efferocytosis. In <em>vivo</em>, the composite PA promotes periodontitis resolution and regeneration. This study provided an easily adjustable supermolecular system enhancing efferocytosis and revealed insights into the relationship between physicochemical properties and biological effects.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 601-615"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818595","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":"Corrigendum to “Versatile self-assembled near-infrared SERS nanoprobes for multidrug-resistant bacterial infection-specific surveillance and therapy” [Acta Biomaterialia 2024, 189, 559-573]","authors":"Qian Gao ,&nbsp;Ruocan Liu ,&nbsp;Yundi Wu ,&nbsp;Fuxiang Wang ,&nbsp;Xilong Wu","doi":"10.1016/j.actbio.2025.08.029","DOIUrl":"10.1016/j.actbio.2025.08.029","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 743-746"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982035","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":"One-step solid phase reaction-induced hydroxyapatite/magnesian whitlockite bioceramics for enhanced bone regeneration","authors":"Ruiqi Mao ,&nbsp;Yu Yang ,&nbsp;Dongxuan Li ,&nbsp;Yawen Huang ,&nbsp;Fengxiong Luo ,&nbsp;Xiang Ge ,&nbsp;Fuzeng Ren ,&nbsp;Qing Jiang ,&nbsp;Kefeng Wang ,&nbsp;Yujiang Fan ,&nbsp;Xingdong Zhang","doi":"10.1016/j.actbio.2025.08.058","DOIUrl":"10.1016/j.actbio.2025.08.058","url":null,"abstract":"<div><div>Regenerative bioceramics for bone repair require an optimal balance of mechanical properties and osteogenic activity. Achieving this dual enhancement remains a significant challenge, particularly regarding the intrinsic properties of the ceramic. This study introduces a one-step solid-phase reaction strategy to generate new phase and nanostructure to enhance the performance of hydroxyapatite (HA) ceramic for bone repair. By incorporating magnesium phosphates (MP), the new phase (magnesian whitlockite, MWH) was produced, which exhibit suitable Mg²⁺ release and degradation efficiency compared to pure HA. The formation of interlaced nanocrystalline structure significantly improved the mechanical properties of the ceramics through a ‘grain binding strengthening’ mechanism, facilitating a transition from intergranular to transgranular fracture modes. Furthermore, MWH crystals with better strength than HA, contributed to the overall mechanical performance, ensuring compatibility with the mechanical requirements of bone implantation. The favorable release kinetics of Mg²⁺ promoted adhesion, spreading, and osteogenic differentiation of bone marrow stromal cells (BMSCs). In vivo studies validated the satisfactory bone regeneration capabilities of HA/MWH bioceramics. This innovative approach achieves a synergistic enhancement of mechanical strength and osteogenic activity, providing valuable insights for the optimization of porous bioceramics and their application in bone regeneration.</div></div><div><h3>Statement of Significance</h3><div>We present an innovative method to conveniently improve the synergistic performance of both mechanical strength and osteogenic activity in bioceramics. A one-step solid phase reaction was developed to produce Hydroxyapatite (HA)/Magnesian Whitlockite (MWH) dual-phase bioceramics, which exhibit superior mechanical properties over popular HA bioceramics. And the more favorable functional Mg²⁺ release kinetics of MWH resulted in a marked enhancement of osteogenic properties. We conducted experiments, computer simulations, cellular and animal evaluations to meticulously investigate the interlaced nanocrystalline structure, the ‘grain binding strengthening’ mechanisms of mechanical enhancement, and the improvement of osteogenic properties. Our work covers the entire spectrum of material science, preparation techniques, and biological performance validation. It provides new scientific insights for the research of porous bioceramics and would promote their applications in bone regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 672-686"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982115","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":"Corrigendum to “Biodegradable oxygen-producing manganese-chelated metal organic frameworks for tumor-targeted synergistic chemo/photothermal/photodynamic therapy” [Acta Biomaterialia 138, 2022, 463–477]","authors":"Lei Feng,&nbsp;Mengyao Chen,&nbsp;Ruihao Li,&nbsp;Lulu Zhou,&nbsp;Chunhui Wang,&nbsp;Pingting Ye,&nbsp;Hu Xiaochun,&nbsp;Jingxian Yang,&nbsp;Yanting Sun,&nbsp;Zhounan Zhu,&nbsp;Kang Fang,&nbsp;Keke Chai,&nbsp;Shuo Shi,&nbsp;Chunyan Dong","doi":"10.1016/j.actbio.2025.07.001","DOIUrl":"10.1016/j.actbio.2025.07.001","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 741-742"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661249","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":"Corrigendum to “Decellularized periosteum as a potential biologic scaffold for bone tissue engineering” [Acta Biomaterialia 2015, 19, 46-55]","authors":"Kai Chen ,&nbsp;Xianfeng Lin ,&nbsp;Qi Zhang ,&nbsp;Jinhu Ni ,&nbsp;Jianmin Li ,&nbsp;Jian Xiao ,&nbsp;Yang Wang ,&nbsp;Yiheng Ye ,&nbsp;Li Chen ,&nbsp;Keke Jin ,&nbsp;Lei Chen","doi":"10.1016/j.actbio.2025.06.040","DOIUrl":"10.1016/j.actbio.2025.06.040","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 737-738"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593156","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":"Imaging the mechanical properties of a developing embryonic tendon using Brillouin microscopy","authors":"Divya Sivalingam ,&nbsp;Kamryn Henderson ,&nbsp;Aniket Jana ,&nbsp;Phong Nguyen ,&nbsp;Giuliano Scarcelli ,&nbsp;Catherine K. Kuo","doi":"10.1016/j.actbio.2025.08.061","DOIUrl":"10.1016/j.actbio.2025.08.061","url":null,"abstract":"<div><div>Tendon mechanical properties are critical for proper musculoskeletal movement. Yet, current understanding of how tendons develop their mechanical properties remains incomplete. Atomic force microscopy and tensile testing are used to characterize early-stage and late-stage embryonic tendon mechanical properties respectively, but both require contact with the tissue, which can alter or destroy tissue structure or integrity and render the tissue unsuitable for subsequent assays. Brillouin confocal microscopy is an emerging tool used to measure mechanical properties of tissues in an all-optical, contact-free, label-free manner. Here, Brillouin confocal microscopy was successfully implemented to measure chick embryo Achilles tendon mechanical properties, which were then validated by comparisons to previously published tensile modulus data. Significant changes in mechanical properties that occur with development and due to experimentally induced changes in extracellular matrix crosslinking were quantifiable. Brillouin microscopy also detected increasing mechanical heterogeneity of developing tendons. The potential to map the spatial distribution of the mechanical properties of developing extracellular matrix using Brillouin microscopy was demonstrated. Measurement of mechanical properties of the tendon within the limb, and sensitivity to changes in tendon strain imposed by changing ankle flexion demonstrated the potential for Brillouin microscopy to quantify tendon properties in vivo. Collectively, these results provide an exciting first study using Brillouin microscopy for quantitative and spatial mapping of embryonic tendon mechanical properties in an all-optical, label-free manner, which could lead to mechanistic discoveries not possible with conventional mechanical testing methodologies.</div></div><div><h3>Statement of significance</h3><div>Tendon injuries and disorders are problematic, as tendons lack the ability to regenerate, and current clinical solutions are insufficient. Knowledge gained from elucidating how embryonic tendons develop their mechanical properties could be used to inform the development of therapeutics to treat injured or abnormal tendons. However, conventional mechanical testing methods require challenging manipulations of small tissues and render tissues unusable for additional assays. Brillouin microscopy is a powerful technique that can image mechanical properties of tissues in a non-contact and label-free manner, which enables in vivo analysis of mechanical properties. In this study, we show that Brillouin microscopy can image mechanical properties of tendon in developing embryos, thus opening new avenues for investigation into the development of tendon mechanical properties.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 419-432"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981965","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":"Human induced pluripotent stem cell-derived nanovesicles for the treatment of ischemic limb disease","authors":"Yuhua Wei ,&nbsp;Akazha Green ,&nbsp;Bijay Guragain ,&nbsp;Bing Bo ,&nbsp;Yu Jiang ,&nbsp;Hua Zhu ,&nbsp;Jianyi Zhang ,&nbsp;Lei Ye","doi":"10.1016/j.actbio.2025.08.050","DOIUrl":"10.1016/j.actbio.2025.08.050","url":null,"abstract":"<div><div>Critical limb ischemia is an advanced stage of peripheral artery disease, characterized by claudication, ischemic pain, and ulceration. It is a severe condition associated with an increased risk of limb amputation and mortality. Although extracellular vehicles (EVs) secreted by endothelial cells (ECs) or mesenchymal stem cells (MSCs) have shown promise for the treatment of ischemic limb diseases in mice, clinical translation has been limited by the low EV yields from cultured cells. In this study, a hypo-immunogenic human induced pluripotent stem cell (hiPSC) line with β2-microglobulin knockout (^B2MKOhiPSC) was used to manufacture nanovesicles (^B2MKOhiPSC<img>NVs), which are hypo-immunogenic as compared to wild type hiPSC manufactured nanovesicles (^WThiPSC<img>NVs). Notably, over 9500 NVs could be produced from a single hiPSC. The zeta potential of hiPSC<img>NVs was -16.7 mV, as measured by the ZETASIZER Nano series instrument. The NVs exhibited a mean diameter of 115.9 ± 43.5 nm, as determined by Nanosight analysis, and displayed bilayer lipid membranes under transmission electron microscopy. <em>In vitro</em>, both ^WThiPSC<img>NVs and ^B2MKOhiPSC<img>NVs protected human umbilical vein endothelial cells (HUVECs) from hypoxic injury, promoted HUVEC proliferation, and did not induce hemolysis. <em>In vivo,</em> ^B2MKOhiPSC<img>NVs administration significantly improved blood perfusion in ischemic limbs 14 days post-treatment. This was accompanied by a notable increase in mouse endothelial cell (EC) proliferation and neovascularization compared to C57BL mice treated with either a saline injection or ^WThiPSC<img>NVs, without the use of immunosuppressive drugs. Furthermore, intramuscular injections of ^WThiPSC<img>NVs did not cause adverse effects on liver or kidney function<em>.</em> These findings suggest that ^B2MKOhiPSC- NVs represent a promising allogeneic therapeutic approach for the treatment of ischemic limb diseases.</div></div><div><h3>Statement of significance</h3><div>The use of hiPSCs as parental cells can easily scale-up NV production.</div><div>NVs derived from β2 microglobulin-knockout hiPSCs (^B2MKOhiPSC<img>NVs) protect endothelial cells from hypoxic injury and enhance their proliferation.</div><div>In immunocompetent mice, administration of ^B2MKOhiPSC<img>NVs significantly enhanced blood perfusion and promoted neovascularization in ischemic limbs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 648-658"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981980","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":"An in situ fused adhesive with integrated antibacterial and hemostatic functionalities for urgent respiratory fistula sealing and enhanced wound repair","authors":"Wenjie Zhang ,&nbsp;YingYing Yang ,&nbsp;Jialing Li ,&nbsp;Haifeng Shen ,&nbsp;Yi Hu ,&nbsp;Penghui Wang ,&nbsp;Qi Zhao ,&nbsp;Hua Zhong ,&nbsp;Bo Chi","doi":"10.1016/j.actbio.2025.08.062","DOIUrl":"10.1016/j.actbio.2025.08.062","url":null,"abstract":"<div><div>Respiratory fistulas remain clinically challenging in endoscopic treatment due to the absence of convenient non-compressive sealing materials. Here, we developed an <em>in situ</em> self-fused powder adhesive (PP powder) to address this limitation. This material integrates the adaptive conformability of hydrogel microparticles with the pressure-resistant sealing capability of bulk hydrogels via water-triggered self-assembly. The PP powder exploits electrostatic attraction and topological effects between cationic microspheres (PL-TCEP) and polyacrylic acid (PAAc). This design yields strong tissue adhesion (29.7 kPa), robust sealing (24.7 kPa), and inherent antibacterial properties. Additionally, it promotes efficient coagulation by synergistically aggregating blood cells and autoactivating the coagulation cascade. Furthermore, we have rigorously validated those hemostatic, sealing, healing capabilities and translational potential through liver injury models, bronchopleural fistula models, infected wound models and rabbit tracheal fistula models. This multifunctional platform advances emergency fistula management while providing a paradigm for designing biomaterials addressing complex clinical scenarios requiring simultaneous hemostasis, sealing, and antimicrobial action.</div></div><div><h3>Statement of Significance</h3><div>This study introduces a rapidly self-assembled poly(amino acid)-based microgel, formed through dynamic ionic crosslinking between cationic poly(amino acids) and poly(acrylic acid) (PAAc). This microgel exhibits exceptional deliverability through narrow channels and hygroscopic self-assembly capabilities, making it an ideal candidate for endoscopic surgical applications, particularly in sealing respiratory tract fistulas. The engineered microgel demonstrates robust mechanical properties, far exceeding the physiological pressures of human airways. Leveraging the spatial architecture of cationic poly(amino acid) microspheres, the microgel not only exhibits inherent antimicrobial activity but also significantly enhances blood cell aggregation, thereby accelerating clot formation more effectively than commercial hemostatic powders. Furthermore, owing to its outstanding biocompatibility, the microgel shows great promise in visceral hemostasis and tissue regeneration, highlighting its potential for advanced biomedical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 362-371"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981995","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":"Impact of the intracellular mechanical microenvironment of breast cancer and normal mammary epithelial cells on magnetic hyperthermia of Fe3O4 nanoparticles","authors":"Man Wang ,&nbsp;Huajian Chen ,&nbsp;Rui Sun ,&nbsp;Tianjiao Zeng ,&nbsp;Chengyu Lu ,&nbsp;Toru Yoshitomi ,&nbsp;Hiroaki Mamiya ,&nbsp;Masaki Takeguchi ,&nbsp;Naoki Kawazoe ,&nbsp;Yingnan Yang ,&nbsp;Guoping Chen","doi":"10.1016/j.actbio.2025.08.031","DOIUrl":"10.1016/j.actbio.2025.08.031","url":null,"abstract":"<div><div>Magnetic hyperthermia has been widely investigated as a promising cancer treatment modality. Efficient heat generation by magnetic nanoparticles under an alternating magnetic field (AMF) is critical for therapeutic efficacy. While extracellular conditions in the tumor microenvironment are considered key determinants of heat generation, the impact of the intracellular microenvironment has received less attention. This study aimed to elucidate how cytoskeletal architecture and intracellular mechanical properties—key components of the intracellular microenvironment—affect the heat generation and hyperthermia efficiency of magnetic Fe₃O₄ nanoparticles (Fe₃O₄ NPs) in human breast carcinomas and normal human mammary epithelial cells. Under AMF exposure, identical amounts of internalized Fe₃O₄ NPs produced different heating effects in the two cell types, resulting in differential magnetic hyperthermia efficiency. Fe₃O₄ NPs internalized by breast carcinomas produced greater temperature increase and induced apoptosis more effectively than those in normal mammary epithelial cells. Moreover, alternating current susceptibility analysis revealed that the softer intracellular cytoskeletal mechanics of breast carcinomas enhanced magnetothermal conversion compared with that of normal mammary epithelial cells. These findings highlight the critical role of intracellular cytoskeletal mechanics in regulating the magnetothermal behavior of Fe₃O₄ NPs during magnetic hyperthermia.</div></div><div><h3>Statement of Significance</h3><div>This study reveals the critical role of the intracellular mechanical microenvironment of breast cancer cells in magnetothermal conversion of magnetic nanoparticles. Breast cancer cells have less organized cytoskeletal structure and softer intracellular microenvironment that are inherently more conducive to the magnetothermal conversion and heating performance of Fe₃O₄ NPs than normal cells. Fe₃O₄ NPs internalized by breast cancer cells generate higher local temperatures and induce significantly greater apoptotic effects. These findings highlight the breast cancer cell intracellular microenvironment as a key determinant in the effectiveness of magnetic hyperthermia, offering new insights into the design and optimization of nanoparticle-based cancer therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 634-647"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982040","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}