Cheng Yang , Shaoshuai Song , Xianhao Zhou , Dejian Li , Chenyang Xu , Chaohong Yu , Guantong Sun , Kaili Lin , Youzhuan Xie
{"title":"Controlled releasing melatonin nanoparticles promote restoration of nucleus pulposus cell homeostasis for alleviating intervertebral disc degeneration","authors":"Cheng Yang , Shaoshuai Song , Xianhao Zhou , Dejian Li , Chenyang Xu , Chaohong Yu , Guantong Sun , Kaili Lin , Youzhuan Xie","doi":"10.1016/j.mtbio.2025.101994","DOIUrl":"10.1016/j.mtbio.2025.101994","url":null,"abstract":"<div><div>The intervertebral administration of anti-inflammatory drugs is a promising local delivery approach to the intervertebral disc integrity restoration for treatment of intervertebral disc degeneration (IVDD), whereas the fast drug clearance in an intervertebral space is always a troublesome issue for the local drug delivery. In this study, we have developed a zeolitic imidazolate framework 8 (ZIF-8) nanoplatform with pH-sensitive property to load melatonin molecules (MT), a hormone with anti-inflammatory and anti-oxidative effects. Thus-synthesized MT@ZIF-8 nanoparticles not only showed good cytocompatibility and pH-dependent drug releasing behavior, but also effectively decreased the intracellular reactive oxygen species level and inhibited the pro-inflammatory cytokine expression for <em>in vitro</em> nucleus pulposus cell (NPC) culture under lipopolysaccharide (LPS) stimulus. Additionally, it was found that NF-κB and MAPK signal pathways are significantly suppressed by the MT@ZIF-8 nanoparticles for the LPS-treated NPCs, revealing the underlying mechanism of restoring extracellular matrix synthesis of the LPS-treated NPCs by the MT@ZIF-8 nanoparticles. Last but not least, the recovery of intervertebral disc components and integrity were observed on a rat caudal IVDD model after injection of the MT@ZIF-8 nanoparticles into the intervertebral space. In brief, this work offered a promising local delivery strategy and a controlled releasing nanoplatform for the applications of melatonin in the IVDD therapy, which we think may have beneficial effects for future clinical treatment of low back pain caused by the IVDD.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101994"},"PeriodicalIF":8.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329694","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}
Daniel Abella-López, Adrián López-Teijeiro, Tomás Pose-Boirazian , Natalia Barreiro-Piñeiro, José M. Martínez-Costas
{"title":"Nanoencapsulation platform for oral delivery of peptides: In vitro stabilization of AvPAL and formulation of a gastrointestinal-resistant luciferase","authors":"Daniel Abella-López, Adrián López-Teijeiro, Tomás Pose-Boirazian , Natalia Barreiro-Piñeiro, José M. Martínez-Costas","doi":"10.1016/j.mtbio.2025.101987","DOIUrl":"10.1016/j.mtbio.2025.101987","url":null,"abstract":"<div><div>Phenylketonuria (PKU) is a genetic metabolic disorder caused by an enzyme deficiency that leads to the accumulation of phenylalanine, which can cause neurotoxicity and several other problems. A potential alternative to the universal standard treatment based on a lifelong protein-restricted diet, is the development of oral replacement therapies using phenylalanine ammonia lyase from <em>Anabaena variabilis</em> (AvPAL). However, oral administration of polypeptides presents a major challenge due to gastrointestinal (GI) instability. To address this issue, the use of the IC-Tagging system as an advanced one step, <em>in cellulo</em> nanosphere (NS)-encapsulation strategy for protein stabilization and oral delivery is proposed. A highly active version of AvPAL was produced to which nanoencapsulation provides formidable thermostability, resistance to acidic pH, long-term storage stability and protection against proteolytic degradation. This latter characteristic, essential for oral delivery of polypeptides, is further enhanced by coating with chitosan the NS-encapsulated enzyme. Thus, a similarly nanoencapsulated and chitosan-coated luciferase displays sustained enzymatic activity through the entire GI transit when administered orally in mice, indicating the high protective capability of the system while maintaining the availability of the enzyme. Overall, these results highlight the potential and versatility for peptide-based oral delivery applications of this innovative methodology.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101987"},"PeriodicalIF":8.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306790","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}
Lili Ma , Yu Yang , Ting Chen , Lizhong Ma , Qilong Deng
{"title":"Developing an NT3-loaded exosomal biodegradable conductive hydrogel combined with EA for targeted treatment of spinal cord injury","authors":"Lili Ma , Yu Yang , Ting Chen , Lizhong Ma , Qilong Deng","doi":"10.1016/j.mtbio.2025.101988","DOIUrl":"10.1016/j.mtbio.2025.101988","url":null,"abstract":"<div><div>Spinal cord injury (SCI) causes permanent sensory and motor function loss below the injury site, with limited treatment options. Conductive hydrogels have shown promise for SCI repair due to their electrical and mechanical properties, while neurotrophic factors and extracellular vesicles exhibit anti-inflammatory and neurorestorative effects. This study developed a dual-loaded conductive hydrogel (Exo-N/NT3@ICH) containing both neurotrophic factors and extracellular vesicles and evaluated its efficacy combined with electroacupuncture (EA) for SCI treatment. The hydrogel was synthesized through Schiff base reactions using oxidized hyaluronic acid and aniline trimer, creating a physically crosslinked, injectable conductive matrix. Assessments examined the hydrogel's morphology, mechanical and electrical properties, swelling, degradation, drug release, and electrochemical behaviour. In vitro and in vivo studies further investigated its biocompatibility, anti-inflammatory effects, and pro-angiogenic potential. Results showed that Exo-N/NT3@ICH enhanced cell proliferation and differentiation through its conductivity, controlled release, and antioxidant properties. In a rat SCI model, the hydrogel improved functional outcomes, attributed to its neurotrophic and neuroregenerative effects. This study highlights Exo-N/NT3@ICH, when combined with EA, as a potential injectable therapeutic system to promote neurogenesis and tissue regeneration after SCI.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101988"},"PeriodicalIF":8.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297297","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}
Fei Sun , Yibo Shan , Shu Pan , Yi Lu , Zhiming Shen , Jianwei Zhu , Lei Yuan , Qi Wang , Wenxuan Chen , Hao Chen , Hongcan Shi
{"title":"In situ vascularization and epithelialization of segmental bioengineered trachea based on marrow-derived stem/progenitor cells","authors":"Fei Sun , Yibo Shan , Shu Pan , Yi Lu , Zhiming Shen , Jianwei Zhu , Lei Yuan , Qi Wang , Wenxuan Chen , Hao Chen , Hongcan Shi","doi":"10.1016/j.mtbio.2025.101990","DOIUrl":"10.1016/j.mtbio.2025.101990","url":null,"abstract":"<div><div>The success of tracheal transplantation depends on the rapid establishment of vascularization and epithelialization to support functional tissue formation. This study presents an innovative approach for in situ transplantation of a biomimetic tracheal graft, integrating microvascularization and epithelialization. First, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) were isolated and purified from bone marrow, serving as seed cells for graft vascularization and epithelialization. Next, 3D printing was employed to create a bilayered tracheal graft using poly(ε-caprolactone) (PCL) and decellularized tracheal extracellular matrix (dtECM), which provided both optimal biomechanical properties and angiogenic potential. MSCs and EPCs were seeded on the inner and outer surfaces of the graft, respectively, and implanted in a long-segment in situ transplantation model. Six months post-transplantation, CT scans revealed a patent luminal space, bronchoscopy confirmed successful anastomosis, scanning electron microscopy showed abundant cilia on the inner graft surface, and α-SMA immunofluorescence demonstrated significant neovascularization. The PCL/dtECM graft exhibited excellent biomechanical properties, along with enhanced cell adhesion and proliferation. The combination of EPCs and MSCs effectively promoted both vascularization and epithelialization, ensuring successful graft integration and long-term survival of the experimental animals.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101990"},"PeriodicalIF":8.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322735","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}
Muhammad Noman , Usman Ijaz , Temoor Ahmed , Zhongna Hao , Jing Wang , Yingying Cai , Yanli Wang , Mohammad Shafiqul Islam , Jason C. White , Jiaoyu Wang
{"title":"Nanohybrid-enabled smart platforms for biostimulation and immunoengineering of plants","authors":"Muhammad Noman , Usman Ijaz , Temoor Ahmed , Zhongna Hao , Jing Wang , Yingying Cai , Yanli Wang , Mohammad Shafiqul Islam , Jason C. White , Jiaoyu Wang","doi":"10.1016/j.mtbio.2025.101989","DOIUrl":"10.1016/j.mtbio.2025.101989","url":null,"abstract":"<div><div>Conventional agricultural practices have become increasingly impractical due to their high inefficiency and overuse, posing serious threats to ecosystem stability and health. Nanohybrids refer to a class of composite materials comprised of nanomaterials combined with diverse materials, including inorganic, polymeric, or biological materials, resulting in hybrid structures with unique functional features such as greater mechanical strength, catalytic activity, and biocompatibility, thus providing advanced frameworks with a vast variety of applications in the agriculture sector. Nanohybrids can augment the functional capabilities of plants, such as photosynthesis and stress tolerance, enabling crops to thrive under diverse climatic conditions. Additionally, nanohybrid-based agricultural practices can improve growth and productivity of crops by providing them with essential nutrients in a more controlled and precise manner. Importantly, nanohybrid-based systems can shield plants against biotic (pest and pathogen attacks) and abiotic (drought, salinity, temperature, and pH etc.) stressors by activating sophisticated, interconnected, and intricate antioxidative or genetic defense responses. Here, we provide a critical overview of nanohybrid-enabled strategies for improving agriculture practices and plant health under biotic and abiotic environmental challenges. We also highlight the transformative potential of nanohybrid-based smart agrochemicals for developing sustainable and eco-stable agricultural systems, thereby ensuring global food security.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101989"},"PeriodicalIF":8.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338522","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":"DFO-loaded PDA nanoparticles facilitated 3D stem cell spheroids for diabetic wound repair by normalizing the pathological microenvironment","authors":"Tong Luo , Peijun Zhu , Shuai Li , Maolin Qin , Zeyu Fang , Fangfang Wu , Qian Wu , Suhong Lu , Yinhe Zhang , Yuli Chen , Junhua Zhou , Daqing Chen , Liangliang Yang , Hongyu Zhang","doi":"10.1016/j.mtbio.2025.101973","DOIUrl":"10.1016/j.mtbio.2025.101973","url":null,"abstract":"<div><div>Diabetic wounds represent a prevalent and challenging complication of diabetes, characterized by compromised immune function, chronic inflammation, oxidative stress, and impaired revascularization, all of which impede normal wound healing. Despite the high therapeutic potential of 3D stem cell spheroids, owing to their structural and functional advantages, the complex microenvironment encountered post-transplantation significantly diminishes their survival and efficacy. This study presents a novel therapeutic strategy that integrates three-dimensional adipose-derived stem cell spheroids (3D-ADSCs) with desferrioxamine-loaded mesoporous polydopamine nanoparticles (M@D), encapsulated within a gelatin methacrylamide (GelMA) hydrogel scaffold, creating a functional bio-composite. The M@D nanoparticles are designed to scavenge reactive oxygen species (ROS) and provide sustained release of desferrioxamine mesylate (DFO), thereby mitigating oxidative stress, fostering angiogenesis, and improving the local wound microenvironment. This enhanced environment significantly promotes the survival, paracrine activity, and regenerative capacity of 3D-ADSCs spheroids. In turn, these spheroids exert potent paracrine, anti-inflammatory, and immunomodulatory effects, pivotal in tissue repair. The synergistic interaction between M@D nanoparticles and 3D-ADSCs within the GelMA hydrogel not only alleviates oxidative stress-induced cellular damage but also enhances vascularization and nutrient supply, thereby accelerating diabetic wound healing. These results underscore the promising potential of combining cell therapy with material science to develop innovative approaches for diabetic wound management.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101973"},"PeriodicalIF":8.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306786","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":"Curcumin-loaded nanoparticles for renal ischemia-reperfusion injuries: Triple-play of redox homeostasis accommodation, lipid metabolism regulation, and nuclear magnetic tracing","authors":"Ning Wang , Xuna Xue , Zhibo Zhang , Meng Gao , Lianhong Yin , Lina Xu , Xuerong Zhao , Jinyong Peng","doi":"10.1016/j.mtbio.2025.101986","DOIUrl":"10.1016/j.mtbio.2025.101986","url":null,"abstract":"<div><div>Renal ischemia reperfusion (RI/R) injury is a significant pathological process that occurs in acute kidney injury (AKI), and is associated with high mortality rates and poor prognoses. It is therefore essential to explore new therapeutic strategies to enhance treatment outcomes for this condition. Curcumin (Cur), a natural bioactive polyphenolic compound, possesses anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor water solubility and low bioavailability. To overcome these challenges, two amphiphilic molecules were synthesized, PEG-DTPA-DA (PD) and Gd-DTPA-N10 (G). By self-assembling PD and G while loading Cur, a nanoparticle was successfully prepared, PDG@Cur, which served three functions: regulation of lipid metabolism, maintenance of redox homeostasis, and function as a nuclear magnetic resonance (NMR) tracer. <em>In vitro</em> and <em>in vivo</em> experiments indicated that PDG@Cur exhibited excellent stability, effectively quenching reactive oxygen species (ROS), and demonstrating robust capabilities for NMR imaging. Furthermore, PDG@Cur mitigated renal tissue damage due to its potent antioxidant properties and ability to regulate lipid metabolism. Molecular mechanism studies revealed that Cur directly bound to FABP4, and that PDG@Cur targeted the FABP4/PPARγ pathway to exert pharmacological effects against RI/R injuries. In conclusion, this study may provide a novel therapeutic strategy for the treatment of RI/R injuries.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101986"},"PeriodicalIF":8.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306791","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}
Bojan Kopilovic , Nabila Laroui , Mathieu Berchel , Paul-Alain Jaffrès , Patrick Midoux , Mara G. Freire , Chantal Pichon
{"title":"Maltodextrin-modified lipoplexes for enhanced mucosal penetration and efficient mRNA delivery","authors":"Bojan Kopilovic , Nabila Laroui , Mathieu Berchel , Paul-Alain Jaffrès , Patrick Midoux , Mara G. Freire , Chantal Pichon","doi":"10.1016/j.mtbio.2025.101975","DOIUrl":"10.1016/j.mtbio.2025.101975","url":null,"abstract":"<div><div>Efficient delivery of messenger ribonucleic acid (mRNA) to mucosal tissues represents a promising approach for localized protein production in the nasal and respiratory tract. Here, we investigate the use of maltodextrin (MDX) as a surface modifier to enhance the delivery of mRNA-loaded histidylated lipoplexes (LXs) to airway epithelial cells. By reducing hydrophobicity, MDX facilitates better penetration through the mucus layer, enabling effective mRNA delivery. MDX-coated LXs improve mRNA delivery and expression <em>in vitro</em> by increasing cellular uptake and supporting sustained protein production. Additionally, MDX incorporation stabilizes in-house-formulated lipoplexes and modulates their interactions with mucin-covered cells. Notably, MDX-coated mRNA LXs display a four-fold increased transfection efficiency, and the protein expression is maintained up to 48 h post-transfection. Furthermore, intranasal administration of MDX-LXs results in efficient gene expression <em>in vivo</em>. Overall, our findings reveal that integrating MDX into mRNA lipoplexes is a promising strategy to advance nasal delivery for gene therapy and protein replacement applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101975"},"PeriodicalIF":8.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313792","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":"γ-glutamyl transpeptidase-catalyzed polymer-enzyme-drug conjugate enhances penetration and suppression in oral squamous cell carcinoma via transdermal application","authors":"Xinyu Zhou , Yiyi Zhang , Jianjun Xiong , Yibin Dai , Fangxing Zhu , Hongtao Sun , Dongwang Zhu , Yingying Huang , Yiran Tan , Xinxia Zhou , Tongchao Zhao , Laiping Zhong , Yichuan Pang , Zhihang Zhou","doi":"10.1016/j.mtbio.2025.101964","DOIUrl":"10.1016/j.mtbio.2025.101964","url":null,"abstract":"<div><div>Over the past century, the treatment of superficial malignant tumors has largely remained within systemic therapies. The major drawback of systemic administration lies in its limited killing effects specifically to superficial tumors while causing potentially severe damage to other organs. Currently, transdermal drug administration for superficial tumors is still minimal, primarily constrained by the poor permeability and specificity in tumorous/precancerous tissue. In this study, we develop an ADC-like nano-medicine utilizing cationization-induced endocytosis and transcytosis. A γ-glutamyl transpeptidase (GGT)-catalyzed polymer-drug conjugate with MMAE payload is synthesized to treat a variety of cancers with elevated GGT expression. For the first time, this research develops a conjugate treating superficial malignant tumors by transdermal administration and names it gaOCD (GGT enzyme-activated oral coating chemotherapeutic drug). Given the superficial nature and the high GGT expression level, oral squamous cell carcinoma (OSCC) is used as a representative to evaluate the efficacy of gaOCD. The electroneutral gaOCD could be cleaved by the highly expressed GGT on OSCC cell membranes. Furthermore, some cationized gaOCD is exocytosed and internalized by neighboring cancer cells to enable deep penetration. The conjugate demonstrates promising anti-tumor efficacy and biosafety when transdermally applied on 4NQO-induced OSCC and intravenously medicated in OSCC transplanted mouse models.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101964"},"PeriodicalIF":8.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297298","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}
Qiancun Hong , Jiajun Huang , Zhiguo Li , Yue Chen , Jiawei Wang , Tongrui Shang , Zelin Chen , Cong Luo , Yongqiang Wang , Xinghong Tang , Taojian Fan , Songyin Huang , Hao Fu , Yandan Yao
{"title":"Efficient on-demand cuproptosis induction against triple-negative breast cancer via dual-responsive black phosphorus nanosheet","authors":"Qiancun Hong , Jiajun Huang , Zhiguo Li , Yue Chen , Jiawei Wang , Tongrui Shang , Zelin Chen , Cong Luo , Yongqiang Wang , Xinghong Tang , Taojian Fan , Songyin Huang , Hao Fu , Yandan Yao","doi":"10.1016/j.mtbio.2025.101985","DOIUrl":"10.1016/j.mtbio.2025.101985","url":null,"abstract":"<div><div>Cuproptosis, a newly identified cell death pathway, has been shown by our analyses to be closely associated with the clinical prognosis of triple-negative breast cancer (TNBC) patients and may potentially facilitate the elimination of TNBC. However, precisely and efficiently regulating cuproptosis in tumor regions in a controllable manner remains challenging. Here, a highly effective cuproptosis inducer based on black phosphorus nanosheets (BPNs@Cu@PDA, denoted as BCP) is constructed, featuring acidic and thermal-responsive copper ion release, as well as enhanced cuprous ion (Cu<sup>+</sup>) loading capability. Briefly, BCP efficiently increases the loading proportion of Cu<sup>+</sup> via inherent surface redox reactions between phosphorus and copper ions (Cu<sup>2+</sup>), thereby enabling a significantly elevated cuproptosis induction ability. After accumulating at the tumor, BCP precisely releases Cu<sup>+/2+</sup> in response to the photo-hyperthermia and acidic microenvironment created by the dopamine modification, thereby efficiently producing reactive hydroxyl radicals (•OH) through Cu<sup>+/2+</sup>-dependent Fenton-like reactions, which leads to significant oxidative damage in TNBC cells. The precisely released Cu<sup>+/2+</sup> further inhibits the production of the Fe-S cluster while causing the aggregation of succinylated proteins, leading to significantly disrupted mitochondrial function and the TCA cycle, thereby inducing significant cuproptosis and subsequent TNBC suppression (over 90 % decrease in tumor volumes) in a synergistic manner. This research presents a novel cuproptosis induction strategy specifically designed for TNBC that has negligible toxicity, which may provide insights into the clinical treatment of TNBC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101985"},"PeriodicalIF":8.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322734","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}