Biomaterials最新文献

{"title":"An artificial-enzyme-equipped immunoregulator blocks platelet-mediated breast cancer hematogenous metastasis","authors":"Ben Hu ,&nbsp;Huimin Lin ,&nbsp;Xiaolong Quan ,&nbsp;Fushan Sun ,&nbsp;Fengling Zhang ,&nbsp;Fang Zhang ,&nbsp;Yu Wang ,&nbsp;Yunhua Chang ,&nbsp;Jigang Wang ,&nbsp;Xiaohui Duan ,&nbsp;Meng Yu","doi":"10.1016/j.biomaterials.2025.123380","DOIUrl":"10.1016/j.biomaterials.2025.123380","url":null,"abstract":"<div><div>Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering \"micro-thrombi,\" CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme <em>in situ</em> releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123380"},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894572","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":"NIR-II imaging guided on-site size variable clustered nanosystem to potentiate sonodynamic therapy in deep-seated tumors","authors":"Qi Yu ,&nbsp;Yujing Zhou ,&nbsp;Qin Zhang ,&nbsp;Juan Li ,&nbsp;Shan Yan ,&nbsp;Jie Xu ,&nbsp;Cao Li ,&nbsp;Xiaobo Zhou ,&nbsp;Yao Sun","doi":"10.1016/j.biomaterials.2025.123381","DOIUrl":"10.1016/j.biomaterials.2025.123381","url":null,"abstract":"<div><div>The insufficient enrichment and penetration of sonosensitizers in the tumor site hamper the antitumor efficiency of sonodynamic therapy (SDT). Herein, tumor-acidity and photothermal controlled nanosystems (NTTD), which coloaded a new type of sonosensitizers, Na₃TiF₆ NPs and second near-infrared (NIR-II) emissive AIEgen (T1), have been developed to achieve highly efficient SDT/photothermal therapy (PTT) in deep-seated tumors. On one hand, NTTD includes ultrasmall Na₃TiF₆ NPs with increased oxygen vacancies, narrow bandgap (2.82 eV) and preferrable absorption capability of H₂O and O₂ molecules, guaranteeing powerful generation of reactive oxygen species (ROS) under US stimulation. On the other hand, with the assistance of the acidic/photothermal responses and deep penetrated NIR-II fluorescence imaging (up to 7 mm), NTTD undergo in situ “two-step” size transformation to achieve enhanced retention and penetration of sonosensitizers in tumor area with high spatiotemporal controllability. In 4T1 tumor model, compared to passive targeting participated NTT group, NTTD elongated the tumor retention time to 60 h and revealed enhanced imaging signal (∼2.4 fold). Further photoirradiation of NTTD assisted ∼4.5-fold enhancement of penetration ability. SDT/PTT synergies have evoked significant ROS generation and tumor inhibition rate of 75.2 % in vivo. This study presents an innovative strategy to exploit novel nano-sonosensitizers with precisely improved tumor accumulation and penetration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123381"},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899040","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":"Gadolinium-ceria hybrid system enables synergistic alleviation of oxidative stress and metabolic thrombo-inflammation for efficient ischemic stroke treatment","authors":"Jin Nan ,&nbsp;Chundongqiu Xia ,&nbsp;Jingyi Zhang ,&nbsp;Yujie Xie ,&nbsp;Shuyu Shi ,&nbsp;Wei Yang ,&nbsp;Meihua Yu ,&nbsp;Yu Chen ,&nbsp;Jun Zhang","doi":"10.1016/j.biomaterials.2025.123379","DOIUrl":"10.1016/j.biomaterials.2025.123379","url":null,"abstract":"<div><div>Ischemic stroke is a primary cause of global death and long-term disability. However, current neuroprotective drugs are far from satisfactory in clinical practice. Compelling evidence has emerged that targeting conjoined multiple factors can bring comprehensive treatment. Herein, we report an image-guided gadolinium-ceria nanoparticle-immobilized small therapeutic molecules (ML265) hybrid system for targeted mitigation of oxidative stress and disruption of metabolic reprogramming in cerebral thrombo-inflammation post ischemic stroke. Sub-10 nm hybrid nanotherapeutics sufficiently extravasate through the blood brain barrier (BBB) to pathological brain area. ML265 effectively obstructs the dimerization of metabolic enzyme (pyruvate kinase muscle 2, PKM2) via NF-κB signaling pathway, thus resulting in a significant reduction in the infiltration of neutrophils, monocytes and macrophages companied with declined production of inflammatory cytokines. Concomitantly, the incorporation of gadolinium into ceria nanoparticles allows enhanced antioxidant capability in alleviation of overproduced radicals, and also confers magnetic resonance imaging (MRI) of the injured brain tissue. The therapy is shown to substantially improve the brain recovery in murine ischemic stroke model. Complemented with great tolerance, this strategy offers a safe and effective strategy for ischemic stroke treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123379"},"PeriodicalIF":12.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894573","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":"α-Synuclein targeted therapy with multiple pathological improvement for Parkinson's disease by macrocyclic amphiphile nanomedicine","authors":"Jian-Mei Gao ,&nbsp;Wen-Bo Li ,&nbsp;Yang Yi ,&nbsp;Jia-Jia Wei ,&nbsp;Miao-Xian Gong ,&nbsp;Bin-Bin Pan ,&nbsp;Xun-Cheng Su ,&nbsp;Yu-Chen Pan ,&nbsp;Dong-Sheng Guo ,&nbsp;Qi-Hai Gong","doi":"10.1016/j.biomaterials.2025.123378","DOIUrl":"10.1016/j.biomaterials.2025.123378","url":null,"abstract":"<div><div>The toxic species formed by the pathological aggregation of α-synuclein (α-Syn) is one of the core pathogenic mechanisms in Parkinson's disease, leading to mitochondrial dysfunction, oxidative stress and ultimately degeneration and loss of dopaminergic neurons. Developing effective inhibitors targeting α-Syn fibrillization critically requires the simultaneous achievement of (1) strong and selective binding of α-Syn for efficient disintegration of fibrils, as well as (2) robust transmembrane capability for efficient cellular uptake. Herein, the co-assembly of guanidinium-modified calixarene (GCA) and cyclodextrin (CD), termed GCA-CD, is screened fully accommodating these conditions. GCA-CD binds tightly and selectively towards α-Syn, thereby effectively inhibiting α-Syn aggregation and disintegrating its fibrils, meanwhile the guanidinium of GCA can additionally improve the transmembrane capability of the co-assembly. <em>In vivo</em> investigations demonstrate that the GCA-CD nanomedicine significantly rescues motor deficits and nigrostriatal degeneration of PD-like rats by decreasing the content of α-Syn as well as restoring mitochondrial dysfunction and suppressing oxidative stress. Astonishingly, transcriptome analysis further reveals the role of GCA-CD in dampening cuproptosis through inhibiting FDX1/LIAS signaling pathway, highlighting the multifaceted therapeutic effects of the co-assembly in PD. The findings in this study underscore the comprehensive exposition on the actual function mechanisms of the therapeutic agents, thereby providing valuable insights for informing material design.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123378"},"PeriodicalIF":12.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899039","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":"Vascular magnifier for ultrahigh-resolution visualization of cerebral vessels in vivo","authors":"Bingjie Li ,&nbsp;Jinbin Pan ,&nbsp;Ruijie Zhang ,&nbsp;Bing Han ,&nbsp;Yujie Zhao ,&nbsp;Guijun Liu ,&nbsp;Yujie Tong ,&nbsp;Yujing He ,&nbsp;Guangchao Xie ,&nbsp;Ruxia Liu ,&nbsp;Ting Zhou ,&nbsp;Quan Zhang ,&nbsp;Shao-Kai Sun","doi":"10.1016/j.biomaterials.2025.123356","DOIUrl":"10.1016/j.biomaterials.2025.123356","url":null,"abstract":"<div><div>High-resolution vascular imaging at tens of micrometers in deep tissues in vivo remains a critical challenge. Ultrahigh field susceptibility-weighted imaging (SWI) holds promise but lacking compatible high-sensitivity imaging probes. Herein, we show a holmium (Ho)-based nanoprobe-enhanced SWI strategy for ultrahigh-resolution imaging of cerebral microvessels at 9.4 T. The polyethylene glycol (PEG)-NaHoF₄ nanoparticles (NPs) fabricated via coprecipitation synthesis combined with PEG modification possess uniform size, appropriate hydrodynamic size (20 nm), good biocompatibility, and long circulation half-life (710 min). Notably, the PEG-NaHoF₄ NPs exhibit high <em>r</em>₂/<em>r</em>₁ (742.7) and T₂∗ relaxivity (<em>r</em>₂∗, 73.16 s⁻¹ mM⁻¹) under 9.4 T due to the large magnetic moment (∼10.6 <em>μ</em>_<em>B</em>) and short electronic relaxation time (∼10⁻¹³ s) of Ho³⁺. The high susceptibility of PEG-NaHoF₄ NPs in blood vessels induces a significant blooming effect, resulting in a magnified vascular appearance on SWI. In vivo high-resolution imaging of cerebral microvessels with diameters as small as 10 μm is achieved using PEG-NaHoF₄ NPs-enhanced SWI under 9.4 T. In two representative brain disease models, glioma and stroke, this nanoprobe enables high-resolution visualization of tumor vasculature and post-stroke collateral circulation, respectively. Our study offers a new paradigm for precise diagnosis of vascular-related diseases, providing a robust tool for their diagnosis, treatment, and prognosis assessment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123356"},"PeriodicalIF":12.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892283","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":"Engineered micro-structured biomimetic material for modelling the outer blood-retinal barrier","authors":"Chloé Dujardin ,&nbsp;Walter Habeler ,&nbsp;Paola Aprile ,&nbsp;Alessandra Dellaquila ,&nbsp;Christelle Monville ,&nbsp;Didier Letourneur ,&nbsp;Teresa Simon-Yarza","doi":"10.1016/j.biomaterials.2025.123357","DOIUrl":"10.1016/j.biomaterials.2025.123357","url":null,"abstract":"<div><div>The outer blood-retinal barrier (oBRB) is compromised in several retinal pathologies, such as age-related macular degeneration affecting over 200 million people worldwide. This 200–350 μm thick tissue includes the retinal pigment epithelium (RPE), the Bruch's membrane, and the vascularized choroid supplying the outer retina. Degeneration of the RPE and/or choroid leads to photoreceptor loss and, ultimately, blindness. Current <em>in vitro</em> co-culture oBRB models developed to better understand the diseases and to propose therapeutic alternatives are often simplistic, focusing on 2D cultures, or face limitations including non-physiological dimensions or low throughput.</div><div>This study presents an innovative scaffold-driven approach to model the oBRB using a polysaccharide membrane engineered by freeze-drying. Our specific protocol allowed to mimic the oBRB structure, within physiological dimensions, generating a non-porous surface to culture the hiPSC-derived RPE monolayer, and an internal 3D porous structure for the choroidal network. Results showed that the inner porous structure promoted physiological self-organization of endothelial cells and pericytes. Our single-piece functional material allowed the cultivation of both RPE and choroidal compartments in close proximity, favoring cellular interactions, while maintaining them in their designated locations. This cyto-compatible, easy-to-use, and off-the-shelf membrane, produced at large amounts and low costs, provides a physiologically relevant biomaterial for oBRB tissue modelling.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123357"},"PeriodicalIF":12.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892284","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":"Smearable CQD-entrapped hydrogel with sensitive pH response and photodynamic antibacterial properties for visual intelligent wound monitoring","authors":"Yun Yuan ,&nbsp;Zirong Li ,&nbsp;Leilei Wu ,&nbsp;Xinyi Cheng ,&nbsp;Chao Deng ,&nbsp;Yuanyuan Yu ,&nbsp;Qiang Wang ,&nbsp;Ping Wang","doi":"10.1016/j.biomaterials.2025.123360","DOIUrl":"10.1016/j.biomaterials.2025.123360","url":null,"abstract":"<div><div>The treatment of chronic wounds remains a significant challenge in the clinical field, and optimizing the treatment plan through visual monitoring of wound healing is an effective way to solve such problem. Herein, we propose a feasible strategy to construct a smearable C–P-T/mCQDs hydrogel for real-time monitoring of wound infection and healing status, through the synergistic combination of modified carbon quantum dots (mCQD), cellulose nanofiber, tannic acid, and polyvinyl alcohol. The hydrogel can be readily applied on the skin and rapidly forms a gel dressing through high-density hydrogen bonding, demonstrating exceptional mechanical robustness (tensile elongation: 600 %) and autonomous self-healing capabilities. In particular, the carboxyl-rich mCQDs are more easily recognized by the sensitive pH-mediated polychromatic fluorescence response under ultraviolet excitation, exhibiting encouraging photodynamic therapy effect against bacterial infections. Under the irradiation of sunlight or near-infrared laser, the hydrogel achieves 99.99 % bactericidal efficacy against multiple types of bacteria (<em>S. aureus, E. coli, P. aeruginosa, A. baumannii</em>) within 20 min through reactive oxygen species generation. Furthermore, C–P-T/mCQDs demonstrates excellent antioxidant activity, biocompatibility, hemostatic efficiency and pro-healing properties. Notably, the mCQD-integrated hydrogel enables real-time, visual monitoring of wound status through its pH-responsive properties, providing substantial translational potential for personalized chronic wound management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123360"},"PeriodicalIF":12.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873558","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":"Manganese-based nanoadjuvants for the synergistic enhancement of immune responses in breast cancer therapy via disulfidptosis-induced ICD and cGAS-STING activation","authors":"Ke Zhang,&nbsp;Chengyao Huang,&nbsp;Yu Ren,&nbsp;Mingyue Zhang,&nbsp;Xiaotong Lu,&nbsp;Bangliu Yang,&nbsp;Peiran Chen,&nbsp;Shiyao Guo,&nbsp;Xueqian Wang,&nbsp;Yuhong Zhuo,&nbsp;Chao Qi,&nbsp;Kaiyong Cai","doi":"10.1016/j.biomaterials.2025.123359","DOIUrl":"10.1016/j.biomaterials.2025.123359","url":null,"abstract":"<div><div>Tumor immunotherapy represents one of the most promising strategies for combating tumors by activating the immune system, harnessing anti-tumor immune cells to eliminate tumor cells, and preventing tumor recurrence and metastasis. However, clinical data indicate that the anti-tumor immune response is often inadequate in many cancer patients, resulting in the failure of tumor immunotherapy. Herein, we report a manganese (Mn)-based nanoadjuvant (denoted as BMP-Au) aimed at synergistically enhancing anti-tumor immune responses in breast cancer therapy through disulfidptosis-induced immunogenic cell death and Mn-mediated cGAS-STING pathway activation. BMP-Au is synthesized using bovine serum albumin as a biotemplate for biomimetic mineralization of manganese phosphate nanosheets, followed by the deposition of gold nanoparticles (Au NPs) on their surface. By exploiting the glucose oxidase-like activity of Au NPs alongside the Fenton-like reaction facilitated by Mn²⁺, BMP-Au orchestrates a cascade catalytic reaction that generates reactive oxygen species from glucose. This process not only initiates disulfidptosis but also leads to DNA fragmentation crucial for activating the cGAS-STING pathway. These concurrent mechanisms compromise cancer cell viability while significantly enhancing tumor immunogenicity, positioning BMP-Au as an innovative nanoadjuvant for cancer treatment that leverages both cellular stress mechanisms and immune activation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123359"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876939","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":"Vascular endothelial growth factor (VEGF) and endogenous calcium-capturing gelatin methacrylate hydrogels promote bone tissue regeneration","authors":"Zhengchao Yuan ,&nbsp;Xinyi Wang ,&nbsp;Peng Li ,&nbsp;Muhammad Shafiq ,&nbsp;Panpan Shang ,&nbsp;Lu Han ,&nbsp;Hao Feng ,&nbsp;Yuan Xu ,&nbsp;Mohamed El-Newehy ,&nbsp;Meera Moydeen Abdulhameed ,&nbsp;Lianyong Jiang ,&nbsp;Xiumei Mo ,&nbsp;Yijiu Ren","doi":"10.1016/j.biomaterials.2025.123352","DOIUrl":"10.1016/j.biomaterials.2025.123352","url":null,"abstract":"<div><div>The regeneration of irregular-shaped bone defects remains a perpetuating challenge. Scaffolds with osteogenesis and angiogenesis dual capabilities hold considerable promise for bone tissue repair. The objective of this study was to delineate the synergistic effect of calcium ions (Ca²⁺)-recruiting peptide (FVDVT, abbreviated as CP) and vascular endothelial growth factor (VEGF)-binding prominin-1-derived peptide (DRVQRQTTTVVA, abbreviated as BP) in gelatin methacrylate (GM)-based hydrogels (GM@BCP). BP-loaded hydrogels can recruit VEGF <em>in situ</em> to promote angiogenesis, as well as promote cell viability and growth as revealed by the whole transcriptome RNA sequencing of human umbilical vein endothelial cells (HUVECs). PLA/G@CP short fibers can induce bone matrix mineralization and regulate mechanical behavior of hydrogels. The GM@BCP hydrogels were found to be cytocompatible, non-toxic, and bioresorbable, as well as fill an irregular-shaped bone defect <em>in vivo</em>. Moreover, evaluation in a rat calverial defect model manifested significant promise of GM@BCP hydrogels to promote bone tissue repair by simultaneously inducing osteogenesis and angiogenesis 8 weeks post-operatively. Taken together, our approach of simultaneously harnessing <em>in situ</em> calcium ion (Ca²⁺) binding and VEGF recruitment may have broad implications for fracture repair and potentially other related disciplines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123352"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886059","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":"Efficacy of benznidazole delivery during Chagas disease nanotherapy is dependent on the nanocarrier morphology","authors":"Debora B. Scariot ,&nbsp;Austeja Staneviciute ,&nbsp;Rayanne R.B. Machado ,&nbsp;Simseok A. Yuk ,&nbsp;Yu-Gang Liu ,&nbsp;Swagat Sharma ,&nbsp;Sultan Almunif ,&nbsp;El Hadji Arona Mbaye ,&nbsp;Celso Vataru Nakamura ,&nbsp;David M. Engman ,&nbsp;Evan A. Scott","doi":"10.1016/j.biomaterials.2025.123358","DOIUrl":"10.1016/j.biomaterials.2025.123358","url":null,"abstract":"<div><div>The causative agent of Chagas disease, the protozoan <em>Trypanosoma cruzi</em>, is an obligate intracellular parasite that is typically treated with daily oral administration of Benznidazole (BNZ), a parasiticidal pro-drug with considerable side effects. Previously, we effectively targeted intracellular parasites using ∼100 nm diameter BNZ-loaded poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) vesicular nanocarriers (a.k.a. polymersomes) in a <em>T. cruzi</em>-infected mouse model, without causing the typical side effects associated with standard BNZ treatment. Here, we exploit the structural versatility of the PEG-b-PPS system to investigate the impact of nanocarrier structure on the efficacy of BNZ nanotherapy. Despite sharing the same surface chemistry and oxidation-sensitive biodegradation, solid core ∼25 nm PEG-b-PPS micelles failed to produce <em>in vivo</em> trypanocidal effects. By applying the Förster Resonance Energy Transfer strategy, we demonstrated that PEG-b-PPS polymersomes promoted sustained intracellular drug release and enhanced tissue accumulation, offering a significant advantage for intracellular drug delivery compared to micelles with the same surface chemistry. Our studies further revealed that the lack of parasiticidal effect in PEG-b-PPS micelles is likely due to their slower rate of accumulation into solid tissues, consistent with the prolonged circulation time of intact micelles. Considering the cardiac damage typically induced by <em>T. cruzi</em> infection<em>,</em> this study also investigated the contributions of cardiac cellular biodistribution and payload release for both nanocarriers to the treatment outcomes of BNZ delivery. Our findings emphasize the crucial role of cardiac macrophages in the parasiticidal effect of BNZ formulations and highlight the critical importance of nanobiomaterial structure during therapeutic delivery.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123358"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894571","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}