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Acta Biomaterialia最新文献

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Sequential delivery of cardioactive drugs via microcapped microneedle patches for improved heart function in post myocardial infarction rats 通过微帽微针贴片序贯给药改善心肌梗死后大鼠心功能。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-15 DOI: 10.1016/j.actbio.2024.12.009
Fengpu He , Syed Muntazir Andrabi , Haiwang Shi , Yura Son , Huiliang Qiu , Jingwei Xie , Wuqiang Zhu
After myocardial infarction, the heart undergoes adverse remodeling characterized by a series of pathological changes, including inflammation, apoptosis, fibrosis, and hypertrophy. In addition to cardiac catheter-based re-establishment of blood flow, patients typically receive multiple medications that aim to address these different mechanisms underlying left ventricular remodeling. The current study aims to establish a versatile multi-drug delivery platform for the controlled and sequential delivery of multiple therapeutic agents in a single treatment. Toward this goal, we generated a microcapped microneedle patch carrying methylprednisolone, interleukin-10, and vascular endothelial growth factor. In vitro characterization demonstrated a time-sequenced release pattern of these drug: methylprednisolone for the first 3 days, interleukin-10 from day 1 to 15, and vascular endothelial growth factor from day 3 to 25. The therapeutic effects of the microneedle patch were evaluated in a rat model of acute myocardial infarction induced by permanent ligation of left anterior descending coronary artery. Heart function was measured using trans-thoracic echocardiography. Heart inflammation, apoptosis, hypertrophy and angiogenesis were evaluated using histology. Our data indicated that, at 28 days after patch transplantation, animals receiving the microneedle patch with sequential release of these three agents showed reduced inflammation, apoptosis and cardiac hypertrophy compared to the animals receiving control patch without sequential release of these agents, which is associated with the improved angiogenesis and heart function. In conclusion, the microneedle patch can be utilized to deliver multiple therapeutic agents in a controlled and sequential manner that aligns with the pathological phases following myocardial infarction.

Statement of significance

The post-myocardial infarction heart remodeling is characterized by a series of pathological events including acute inflammation, apoptosis, fibrosis, cardiac hypertrophy, and depressed heart function. In current clinical practice, multiple procedures and drugs given at different time points are necessary to combat these series of pathological events. In this study, we developed a novel microcapped microneedle patch for the controlled sequential delivery of triple cardioprotective drugs aiming to combat acute inflammation and cardiac hypertrophy, and promote angiogenesis. This study presents a comprehensive therapeutic approach, with the microneedle patch addressing multifaceted pathological processes during post-myocardial infarction left ventricular remodeling. This cardiac drug delivery system has the potential to improve patient treatment by delivering drugs in alignment with the series of time-dependent pathological phases following myocardial infarction, ultimately improving clinical outcomes.
心肌梗死后,心脏发生不良重构,表现为炎症、细胞凋亡、纤维化、肥大等一系列病理改变。除了以心导管为基础的血流重建外,患者通常接受多种药物治疗,旨在解决这些不同的左心室重构机制。目前的研究旨在建立一个多功能的多药递送平台,用于在一次治疗中控制和顺序递送多种治疗药物。为了实现这一目标,我们制作了一个微帽微针贴片,携带甲基强的松龙、白细胞介素-10和血管内皮生长因子。体外表征显示了这些药物的时间顺序释放模式:前3天为甲基强的松龙,第1天至第15天为白介素-10,第3天至第25天为血管内皮生长因子。在冠状动脉左前降支永久性结扎致急性心肌梗死大鼠模型上观察微针贴片的治疗效果。采用经胸超声心动图测量心功能。组织学观察心脏炎症、细胞凋亡、肥大和血管新生。我们的数据表明,在贴片移植后28天,接受这三种药物顺序释放的微针贴片的动物与接受没有顺序释放这些药物的对照贴片的动物相比,炎症、细胞凋亡和心脏肥厚都有所减少,这与血管生成和心脏功能的改善有关。综上所述,微针贴片可以根据心肌梗死后的病理阶段,以可控和顺序的方式输送多种治疗药物。意义声明:心肌梗死后心脏重构以急性炎症、细胞凋亡、纤维化、心肌肥厚、心功能下降等一系列病理事件为特征。在目前的临床实践中,需要在不同的时间点给予多种治疗和药物来对抗这一系列的病理事件。在这项研究中,我们开发了一种新型的微帽微针贴片,用于控制三重心脏保护药物的顺序递送,旨在对抗急性炎症和心脏肥厚,并促进血管生成。本研究提出了一种综合治疗方法,微针贴片处理心肌梗死后左心室重构过程中的多方面病理过程。这种心脏给药系统有可能通过根据心肌梗死后一系列时间依赖性病理阶段给药来改善患者的治疗,最终改善临床结果。
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引用次数: 0
X-ray triggered bimetallic nanoassemblies as radiosensitizers and STING agonists for a CDT/radio-immunotherapy strategy X 射线触发双金属纳米组件作为 CDT/放射免疫疗法战略的放射增敏剂和 STING 激动剂。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-15 DOI: 10.1016/j.actbio.2024.12.030
Ruifang Chen , Jinglang Gong , Ziyi Yu , Xiyao Wu , Changjun Li , Yiling Ruan , Shouju Wang , Xiaolian Sun
Radiotherapy (RT) is a cornerstone of cancer therapy, but its effectiveness is constrained by dose-limiting toxicity and inadequate systemic immune activation. To overcome these limitations, we have engineered an X-ray-responsive nanoassembly (sMnAu NAs) by cross-linking monodisperse MnAu nanoparticles (NPs) with radiation-responsive diselenide-containing linkers. MnAu alloy NPs not only provide Au NPs for radiosensitization, but also control Mn (0) release, which stimulates Fenton-like reaction for chemodynamic therapy and is transferred into Mn2+ to activate the STING pathway for immunotherapy. The responsive design not only improves tumor accumulation via EPR effect during circulation, but also achieves deep penetration of MnAu NPs following X-ray induced disassembly. The synergistic combination of chemodynamic therapy, radiotherapy and immunotherapy exhibits remarkable inhibition of tumor growth and metastasis. Overall, our sMnAu NAs represent a promising radiosensitizer for chemodynamic therapy and radiotherapy to enhance immunotherapy.

Statement of Significance

As a principal treatment modality in cancer management, RT is limited due to the co-irradiation of organs at risk and subsequent normal tissue toxicities. This study reported an X-ray responsive radiosensitizer prepared by cross-linking monodisperse MnAu NPs with diselenide-containing linkers. Upon X-ray irradiation, sMnAu NAs accumulate in tumors and disassemble into MnAu NPs, enabling deeper penetration. The increased surface area of MnAu NPs enhances the exposure of Mn(0), which reacts into Mn2+ and enhances ROS generation. The released Mn2+ activates the STING pathway, potentiating the X-ray-induced immune response. The synergistic integration of CDT, RT, and immunotherapy results in a potent suppression of tumor growth and metastasis. Collectively, this X-ray activatable CDT/radio-immunotherapy strategy holds great potential for effective cancer treatment.
放射治疗(RT)是癌症治疗的基石,但其有效性受到剂量限制性毒性和不充分的全身免疫激活的限制。为了克服这些限制,我们设计了一种x射线响应纳米组件(sMnAu NAs),通过将单分散的MnAu纳米颗粒(NPs)与辐射响应的含二硒化物连接剂交联。MnAu合金NPs不仅为放射线致敏提供Au NPs,还能控制Mn(0)释放,刺激fenton样反应进行化学动力学治疗,并转移到Mn2+中激活STING途径进行免疫治疗。响应式设计不仅在循环过程中通过EPR效应促进肿瘤积累,而且在x射线诱导分解后实现了MnAu NPs的深度穿透。化疗、放疗和免疫联合治疗对肿瘤的生长和转移具有显著的抑制作用。总的来说,我们的sMnAu NAs代表了一种有前途的放射增敏剂,用于化学动力学治疗和放射治疗,以增强免疫治疗。意义声明:作为癌症治疗的主要治疗方式,放疗(RT)由于危险器官的共照射和随后的正常组织毒性而受到限制。本研究报道了一种x射线响应的放射增敏剂,该增敏剂是由单分散的MnAu纳米颗粒(NPs)与含二硒化物的连接剂交联制备的。在x射线照射下,sMnAu纳米组件(NAs)在肿瘤中积累并分解成MnAu纳米组件,从而能够更深地穿透肿瘤。MnAu NPs表面积的增加增加了Mn(0)的暴露,Mn(0)反应成Mn2+,增强了ROS的生成。释放的Mn2+激活STING通路,增强x射线诱导的免疫反应。CDT, RT和免疫治疗的协同整合导致肿瘤生长和转移的有效抑制。总的来说,这种x射线激活CDT/放射免疫治疗策略具有有效治疗癌症的巨大潜力。
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引用次数: 0
Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic Dhvar5- 和 MSI78 涂层钛对耐甲氧西林金黄色葡萄球菌具有杀菌、免疫调节和成骨作用。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.016
B. Costa , J. Coelho , V. Silva , H. Shahrour , N.A. Costa , A.R. Ribeiro , S.G. Santos , F. Costa , G. Martínez-de-Tejada , C. Monteiro , M.C.L. Martins
Infection is one of the major issues associated with the failure of orthopedic devices, mainly due to implant bacterial colonization, biofilm formation, and associated antibiotic resistance. Antimicrobial peptides (AMP) are a promising alternative to conventional antibiotics given their broad-spectrum of activity, low propensity to induce bacterial resistance, and ability to modulate host immune responses. Dhvar5 (LLLFLLKKRKKRKY) and MSI78 (GIGKFLKKAKKFGKAFVKILKK) are two AMP with broad-spectrum activity against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), one of the most problematic etiologic agents in Orthopedic Devices-Related Infections (ODRI). This work aims to evaluate the bactericidal, immunomodulatory and osteogenic potential of Dhvar5- and MSI78-coated titanium surfaces (AMP-Ti). Two AMP-Ti surfaces were successfully obtained by grafting Dhvar5 (0.8 ± 0.1 µM/mm2) or MSI78 (0.5 ± 0.3 µM/mm2) onto titanium substrates through a polydopamine layer. Both AMP-Ti were bactericidal against MRSA, eradicating bacteria upon contact for 6 h in a culture medium supplemented with human plasma proteins. The AMP-Ti immunomodulatory potential was evaluated using human primary macrophages, by assessing surfaces capacity to induce pro-/anti-inflammatory (M1/M2) markers and cytokines. While in naïve conditions both AMP-Ti surfaces slightly promoted the M2 marker CD163, in response to LPS and IFN-γ (simulating a bacterial infection), both AMP increased the M1 marker CCR7 and enhanced macrophage secretion of pro-inflammatory IL-6 and TNF-α cytokines, particularly for Ti-MSI78 surfaces. Additionally, both AMP-Ti surfaces were cytocompatible and promoted osteoblastic cell differentiation. This proof-of-concept study demonstrated the high potential of Dhvar5- and MSI78-Ti as antimicrobial coatings for ODRI prevention.

Statement of significance

This study investigates the bactericidal effects of the antimicrobial peptides Dhvar5 and MSI78, immobilized on titanium (Ti) surfaces through a polydopamine coating, aiming at the prevention of Orthopedic-Device Related Infections (ODRIs). The developed coatings displayed MRSA-sterilizing activity, while revealing an immunomodulatory potential towards macrophages and promoting osteoblastic cell differentiation. This strategy allows a quick and easy immobilization of high quantities of AMP, unlike most other approaches, thus favoring its clinical translation.
感染是骨科设备失效的主要原因之一,主要是由于植入物细菌定植、生物膜形成以及相关的抗生素耐药性。抗菌肽(AMP)具有广谱抗菌活性、诱导细菌耐药性的倾向性低以及调节宿主免疫反应的能力,因此有望成为传统抗生素的替代品。Dhvar5(LLLFLLKKRKRKKY)和 MSI78(GIGKFLKAKKFGKAFVKILKK)是两种具有广谱抗菌活性的 AMP,其中包括耐甲氧西林金黄色葡萄球菌(MRSA),MRSA 是骨科设备相关感染(ODRI)中最棘手的病原体之一。这项研究旨在评估 Dhvar5- 和 MSI78 涂层钛表面(AMP-Ti)的杀菌、免疫调节和成骨潜力。通过聚多巴胺层将 Dhvar5(0.8 ± 0.1 µM/mm2)或 MSI78(0.5 ± 0.3 µM/mm2)接枝到钛基底上,成功获得了两种 AMP-Ti 表面。两种 AMP-Ti 对 MRSA 都有杀菌作用,在添加了人血浆蛋白的培养基中接触 6 小时即可消灭细菌。通过评估表面诱导促/抗炎(M1/M2)标记物和细胞因子的能力,使用人类原代巨噬细胞对 AMP-Ti 的免疫调节潜力进行了评估。在初始条件下,两种 AMP-Ti 表面都能轻微促进 M2 标记 CD163,但在 LPS 和 IFN-γ(模拟细菌感染)的作用下,两种 AMP 都能增加 M1 标记 CCR7,并促进巨噬细胞分泌促炎性 IL-6 和 TNF-α 细胞因子,尤其是 Ti-MSI78 表面。此外,两种 AMP-Ti 表面都具有细胞相容性,并能促进成骨细胞分化。这项概念验证研究证明了 Dhvar5- 和 MSI78-Ti 作为抗菌涂层用于预防 ODRI 的巨大潜力。意义说明:本研究调查了通过聚多巴胺涂层固定在钛(Ti)表面的抗菌肽 Dhvar5 和 MSI78 的杀菌效果,旨在预防骨科器械相关感染(ODRIs)。所开发的涂层具有 MRSA 灭菌活性,同时对巨噬细胞具有免疫调节潜力,并能促进成骨细胞分化。与其他大多数方法不同的是,这种策略可以快速、简便地固定大量 AMP,因此有利于将其应用于临床。
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引用次数: 0
Incorporation of cerium oxide nanoparticles into the micro-arc oxidation layer promotes bone formation and achieves structural integrity in magnesium orthopedic implants 在微弧氧化层中加入氧化铈纳米粒子可促进骨形成,并实现镁骨科植入物的结构完整性。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.008
Guan-Lin Wu , Chin-En Yen , Wei-Chien Hsu , Ming-Long Yeh
Biodegradable metals offer significant advantages by reducing the need for additional surgeries following bone fixation. These materials, with their optimal mechanical and degradable properties, also mitigate stress-shielding effects while promoting biological processes essential for healing. This study investigated the in vitro and in vivo biocompatibility of ZK60 magnesium alloy coated with a micro-arc oxidative layer incorporated with cerium oxide nanoparticles in orthopedic implants. The results demonstrated that the magnesium substrate undergoes gradual degradation, effectively eliminating long-term inflammation during bone formation. The micro-arc oxidative coating forms a dense ceramic layer, acting as a protective barrier that reduces corrosion rates and enhances the biocompatibility of the magnesium substrate. The incorporation of cerium oxide nanoparticles improves the tribological properties of the coating, refining degradation patterns and improving osteogenic characteristics. Furthermore, cerium oxide nanoparticles enhance bone reconstruction by facilitating appropriate interconnections between newly formed bone and native bone tissue. Consequently, cerium oxide nanoparticles contribute to favorable biosafety outcomes and exceptional bone remodeling capabilities by supporting bone healing and sustaining a prolonged degradation process, ultimately achieving dynamic equilibrium in bone formation.

Statement of significance

This study comprehensively examined the incorporation of cerium oxide nanoparticles into biodegradable magnesium through a micro-arc oxidative process for use in orthopedic implants. This study conducted a comprehensive analysis involving material characterization, biodegradability testing, in vitro osteogenesis assays, and in vivo implantation, highlighting the potential benefits of the distinctive properties of cerium oxide nanoparticles. This research emphasizes the ability of cerium oxide nanoparticles to enhance the biodegradability of magnesium and facilitate remarkable bone regeneration, suggesting promising advantages for additive materials in orthopedic implants.
生物可降解金属具有显著优势,可减少骨骼固定后的额外手术需求。这些材料具有最佳的机械和可降解特性,还能减轻应力屏蔽效应,同时促进愈合所必需的生物过程。本研究调查了ZK60镁合金的体外和体内生物相容性,该材料在骨科植入物上涂覆了一层含有氧化铈纳米颗粒的微弧氧化层。结果表明,镁基质会逐渐降解,有效消除了骨形成过程中的长期炎症。微弧氧化涂层形成了致密的陶瓷层,起到了保护屏障的作用,降低了腐蚀率,增强了镁基底的生物相容性。纳米氧化铈颗粒的加入改善了涂层的摩擦学特性,细化了降解模式,提高了成骨特性。此外,纳米氧化铈颗粒还能促进新形成的骨与原生骨组织之间的适当互连,从而加强骨重建。因此,纳米氧化铈粒子通过支持骨愈合和维持长时间的降解过程,最终实现骨形成的动态平衡,有助于实现良好的生物安全结果和卓越的骨重塑能力。意义说明:本研究全面考察了通过微弧氧化工艺将纳米氧化铈颗粒掺入可生物降解的镁中,用于骨科植入物的情况。该研究进行了全面的分析,包括材料表征、生物降解性测试、体外成骨试验和体内植入,突出强调了氧化铈纳米粒子独特性能的潜在优势。这项研究强调了氧化铈纳米粒子增强镁的生物降解性和促进显著骨再生的能力,为骨科植入物添加材料带来了希望。
{"title":"Incorporation of cerium oxide nanoparticles into the micro-arc oxidation layer promotes bone formation and achieves structural integrity in magnesium orthopedic implants","authors":"Guan-Lin Wu ,&nbsp;Chin-En Yen ,&nbsp;Wei-Chien Hsu ,&nbsp;Ming-Long Yeh","doi":"10.1016/j.actbio.2024.11.008","DOIUrl":"10.1016/j.actbio.2024.11.008","url":null,"abstract":"<div><div>Biodegradable metals offer significant advantages by reducing the need for additional surgeries following bone fixation. These materials, with their optimal mechanical and degradable properties, also mitigate stress-shielding effects while promoting biological processes essential for healing. This study investigated the in vitro and in vivo biocompatibility of ZK60 magnesium alloy coated with a micro-arc oxidative layer incorporated with cerium oxide nanoparticles in orthopedic implants. The results demonstrated that the magnesium substrate undergoes gradual degradation, effectively eliminating long-term inflammation during bone formation. The micro-arc oxidative coating forms a dense ceramic layer, acting as a protective barrier that reduces corrosion rates and enhances the biocompatibility of the magnesium substrate. The incorporation of cerium oxide nanoparticles improves the tribological properties of the coating, refining degradation patterns and improving osteogenic characteristics. Furthermore, cerium oxide nanoparticles enhance bone reconstruction by facilitating appropriate interconnections between newly formed bone and native bone tissue. Consequently, cerium oxide nanoparticles contribute to favorable biosafety outcomes and exceptional bone remodeling capabilities by supporting bone healing and sustaining a prolonged degradation process, ultimately achieving dynamic equilibrium in bone formation.</div></div><div><h3>Statement of significance</h3><div>This study comprehensively examined the incorporation of cerium oxide nanoparticles into biodegradable magnesium through a micro-arc oxidative process for use in orthopedic implants. This study conducted a comprehensive analysis involving material characterization, biodegradability testing, in vitro osteogenesis assays, and in vivo implantation, highlighting the potential benefits of the distinctive properties of cerium oxide nanoparticles. This research emphasizes the ability of cerium oxide nanoparticles to enhance the biodegradability of magnesium and facilitate remarkable bone regeneration, suggesting promising advantages for additive materials in orthopedic implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 80-97"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering a nano-drug delivery system to regulate m6A modification and enhance immunotherapy in gastric cancer 利用纳米给药系统调节胃癌中的 m6A 修饰并加强免疫疗法。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.036
Zhengshuo Li , Xiaoyue Zhang , Can Liu , Yangge Wu , Yuqing Wen , Run Zheng , Chenxiao Xu , Junrui Tian , Qiu Peng , Xiang Zheng , Jia Wang , Qun Yan , Lingyu Wei , Jian Ma
Cancer cell membrane-derived nanoparticle drug delivery system enables precise drug delivery to tumor tissues and is a new effective way to treat solid tumors. The aim of this study is to develop a safe and effective cancer cell membrane-derived nano-delivery system targeting gastric cancer. We previously reported that EPH receptor A2 (EphA2) is an important target for gastric cancer. RNA m6A methyltransferases METTL3 is upregulated in multiple cancers and promotes cancer development by increasing the expression of multiple oncogenes. We design a new nano-delivery system PLGA-STM-TAT: nanoparticles PLGA (poly lactic acid-hydroxyacetic acid) loaded with METTL3 inhibitor STM2457 and cell-penetrating peptide TAT, and then covered with gastric cancer cell membranes equipped with YSA peptides by means of click chemistry, which targeting EphA2. The nanoparticles are specifically enriched in gastric cancer tissues, significantly increased drug accumulation, and inhibited cancer cell proliferation by decreasing key oncogenes c-MYC and BRD4. During drug administration, we found that the expression of the immune checkpoint molecule PD-L1 was suppressed, and the anti-tumor immune effect was enhanced by the nano-delivery system in combination with anti-PD1. This cancer cell membrane-derived nano-delivery system provides a new biological strategy to treat gastric cancer through effective m6A modulation and EphA2 targeting.

Statement of significance

M6A modifications have important biological roles, especially in tumors. Targeting highly modified m6A in gastric cancer becomes a challenge. We developed a nano-drug delivery system for modulating m6A that could produce an effective anti-cancer therapeutic effect and that the nanoparticles enhanced antitumor immunity when combined with anti-PD1.This cancer cell membrane-derived new nano-drug delivery system shows great promise as an antitumor approach by modulating m6A modification and targeting EphA2 in gastric cancers.
癌细胞膜衍生纳米颗粒给药系统可将药物精确输送到肿瘤组织,是治疗实体瘤的一种新的有效方法。本研究旨在开发一种安全有效的针对胃癌的癌细胞膜衍生纳米给药系统。此前我们曾报道,EPH受体A2(EphA2)是胃癌的一个重要靶点。RNA m6A甲基转移酶METTL3在多种癌症中上调,并通过增加多种癌基因的表达促进癌症发展。我们设计了一种新的纳米给药系统 PLGA-STM-TAT:纳米颗粒 PLGA(聚乳酸-羟基乙酸)装载有 METTL3 抑制剂 STM2457 和细胞穿透肽 TAT,然后通过点击化学方法将装有 YSA 肽的胃癌细胞膜覆盖,该 YSA 肽靶向 EphA2。该纳米颗粒在胃癌组织中特异性富集,显著增加了药物积累,并通过降低关键癌基因c-MYC和BRD4抑制癌细胞增殖。在给药过程中,我们发现免疫检查点分子PD-L1的表达受到抑制,纳米给药系统与抗PD1联用增强了抗肿瘤免疫效果。这种源自癌细胞膜的纳米递送系统通过有效的 m6A 调节和 EphA2 靶向,为治疗胃癌提供了一种新的生物策略。意义说明:M6A修饰具有重要的生物学作用,尤其是在肿瘤中。在胃癌中靶向高度修饰的 m6A 成为一项挑战。我们开发了一种调节 m6A 的纳米给药系统,该系统能产生有效的抗癌治疗效果,而且当纳米颗粒与抗 PD1 结合使用时,能增强抗肿瘤免疫力。这种由癌细胞膜衍生的新型纳米给药系统通过调节胃癌中的 m6A 修饰和靶向 EphA2 显示出作为抗肿瘤方法的巨大前景。
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引用次数: 0
Expansion limits of meshed split-thickness skin grafts 网状裂厚植皮的扩张极限。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.038
Haomin Yu , Mohammad Jafari , Aliza Mujahid , Chelsea F Garcia , Jaisheel Shah , Riya Sinha , Yuxuan Huang , Delaram Shakiba , Yuan Hong , Danial Cheraghali , John R.S. Pryce , Jacob A. Sandler , Elliot L. Elson , Justin M. Sacks , Guy M. Genin , Farid Alisafaei
Split-thickness skin grafts are widely used to treat chronic wounds. Procedure design requires surgeons to predict how much a patch of the patient's own skin expands when it is meshed with rows of slits and stretched over a larger wound area. Accurate prediction of graft expansion remains a challenge, with current models overestimating the actual expansion, leading to suboptimal outcomes. Inspired by the principles of mechanical metamaterials, we developed a model that distinguishes between the kinematic rearrangement of structural elements and their stretching, providing a more accurate prediction of skin graft expansion. Our model was validated against extensive data from skin graft surgeries, demonstrating vastly superior predictive capability compared to existing methods. This metamaterial-inspired approach enables informed decision-making for potentially improving healing outcomes.

Statement of Significance

Accurately predicting the expansion of meshed skin grafts is crucial for minimizing patient trauma and optimizing healing outcomes in reconstructive surgery. However, current quantitative models, which treat grafts as tessellated trusses of rigid bars, fail to accurately estimate graft expansion. We have uncovered the mechanisms underlying skin graft expansion and developed a straightforward method based on these findings. This method, designed for practical use by surgeons, provides accurate predictions of graft expansion, as validated against extensive data from skin graft surgeries.
裂厚植皮术被广泛用于治疗慢性伤口。手术设计要求外科医生预测病人自己的一块皮肤在被一排排缝隙啮合并拉伸到更大的伤口区域时的扩张程度。准确预测移植皮肤的扩张程度仍是一项挑战,目前的模型高估了实际扩张程度,导致疗效不理想。受机械超材料原理的启发,我们开发了一种模型,它能区分结构元素的运动学重排和拉伸,从而更准确地预测植皮的扩张。我们的模型通过大量植皮手术数据进行了验证,与现有方法相比,预测能力大大提高。这种受超材料启发的方法可帮助人们做出明智的决策,从而改善愈合效果。意义说明:在整形外科手术中,准确预测网状植皮的扩张对于最大限度地减少患者创伤和优化愈合效果至关重要。然而,目前的定量模型将移植物视为由刚性条组成的棋盘格桁架,无法准确估计移植物的扩张。我们揭示了皮肤移植物膨胀的内在机制,并在此基础上开发了一种简单易行的方法。这种方法专为外科医生的实际使用而设计,通过大量植皮手术数据的验证,可以准确预测移植物的扩张情况。
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引用次数: 0
Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation 脱细胞猪真皮水凝胶可增强辐照环境下植入伤口的愈合。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.009
Lillian DeCostanza , Graham M. Grogan , Anthony C. Bruce , Corrina M. Peachey , Evan A. Clark , Kristen Atkins , Tina Tylek , Michael D. Solga , Kara L. Spiller , Shayn M. Peirce , Christopher A. Campbell , Patrick S. Cottler
Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in implant-based breast reconstruction, and has shown to modulate the healing response. However, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective biomaterial integration requires regulating the immune response, fibrosis, and adipocyte-driven functionalization. Extracellular matrix (ECM) hydrogels have demonstrated utility in tissue regeneration, and decreasing inflammation and fibrosis in various tissues. Therefore, we hypothesized that a Decellularized Porcine Dermal (DPD) hydrogel to support ADM integration would prevent excessive fibrosis, regulate the macrophage response, and promote adipogenesis. Exploration of DPD hydrogel during ADM implantation in mice (healthy and radiated) revealed long-term effects of irradiation on implant wound healing. DPD hydrogel rescued radiation-induced fibrosis, restoring capsule thickness of healthy mice, and did not increase the fibroblast migration into the ADM. As a modulating soft tissue filler, DPD hydrogel also promoted adipocyte infiltration in healthy and irradiated mice. Detailed macrophage analysis showed that radiation led to the increase in pro-inflammatory, transition, and reparative markers. Despite relatively subtle effects on individual macrophage phenotype markers, multidimensional flow cytometry analysis revealed that DPD hydrogel temporally regulated two subpopulations. he presence of DPD resulted in significantly reduced CD9HiArg1HiCD301bLo and CD163HiCD38HiCD301bHi macrophages in healthy mice at one week, and a significant increase in CD9High macrophages with low expression of other markers at 6 weeks in irradiated mice. DPD hydrogel promotes a decreased fibrotic, and adipocyte-promoting coordination of wound healing in healthy and irradiated wound beds while not disrupting the immunomodulatory effects of ADM.

Statement of significance

Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in post-mastectomy implant-based breast reconstruction, and positively affects wound healing. Following breast reconstruction, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective wound healing and biomaterial integration requires regulating the cellular immune response. Extracellular matrix hydrogels have demonstrated utility in tissue regeneration and decreasing inflammation and fibrosis in various tissues, but has yet to be utilized in the setting of breast reconstruction. Here, we demonstrated that a decellularized dermal hydrogel as an adjunct to ADM, decreases fibrosis and promotes adipogenesis during the coordination of wound healing in healthy and clinically relevant microenvironments that have received radiation therapy while not disrupting the immunomodulatory effects of implanted ADM.
细胞真皮基质(ADM)可为植入物乳房重建提供机械和软组织支持,并可调节愈合反应。然而,.皮瓣坏死、水肿和之前的放射治疗会阻碍 ADM 的整合。有效的生物材料整合需要调节免疫反应、纤维化和脂肪细胞驱动的功能化。细胞外基质(ECM)水凝胶已在组织再生、减少各种组织的炎症和纤维化方面发挥了作用。因此,我们假设用猪真皮脱细胞(DPD)水凝胶支持 ADM 整合可防止过度纤维化、调节巨噬细胞反应并促进脂肪生成。在小鼠(健康小鼠和辐射小鼠)体内植入 ADM 期间对 DPD 水凝胶进行的研究表明,辐照对植入伤口愈合有长期影响。DPD 水凝胶可修复辐射诱导的纤维化,恢复健康小鼠的囊厚度,并且不会增加成纤维细胞向 ADM 的迁移。作为一种调节性软组织填充物,DPD 水凝胶还能促进健康小鼠和辐照小鼠体内脂肪细胞的浸润。详细的巨噬细胞分析表明,辐射导致促炎、过渡和修复标志物增加。尽管对单个巨噬细胞表型标志物的影响相对微小,但多维流式细胞术分析表明,DPD 水凝胶在时间上调节了两个亚群。DPD 的存在导致健康小鼠的 CD9HiArg1HiCD301bLo 和 CD163HiCD38HiCD301bHi 巨噬细胞在一周时显著减少,而辐照小鼠的 CD9High 巨噬细胞在六周时显著增加,其他标志物的表达量较低。DPD 水凝胶可减少纤维化,促进脂肪细胞在健康和辐照伤口床的伤口愈合中的协调作用,同时不会破坏 ADM 的免疫调节作用。意义说明:细胞真皮基质(ADM)为乳房切除术后植入假体的乳房重建提供机械和软组织支持,并对伤口愈合产生积极影响。乳房重建后,皮瓣坏死、水肿和之前的放射治疗会阻碍 ADM 的整合。有效的伤口愈合和生物材料整合需要调节细胞免疫反应。细胞外基质水凝胶在组织再生、减少各种组织的炎症和纤维化方面已被证明是有用的,但在乳房重建中尚未得到应用。在这里,我们证明了一种脱细胞真皮水凝胶作为 ADM 的辅助材料,可以在接受过放射治疗的健康和临床相关微环境中,在协调伤口愈合的过程中减少纤维化并促进脂肪生成,同时不会破坏植入 ADM 的免疫调节作用。
{"title":"Decellularized porcine dermal hydrogel enhances implant-based wound healing in the setting of irradiation","authors":"Lillian DeCostanza ,&nbsp;Graham M. Grogan ,&nbsp;Anthony C. Bruce ,&nbsp;Corrina M. Peachey ,&nbsp;Evan A. Clark ,&nbsp;Kristen Atkins ,&nbsp;Tina Tylek ,&nbsp;Michael D. Solga ,&nbsp;Kara L. Spiller ,&nbsp;Shayn M. Peirce ,&nbsp;Christopher A. Campbell ,&nbsp;Patrick S. Cottler","doi":"10.1016/j.actbio.2024.11.009","DOIUrl":"10.1016/j.actbio.2024.11.009","url":null,"abstract":"<div><div>Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in implant-based breast reconstruction, and has shown to modulate the healing response. However, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective biomaterial integration requires regulating the immune response, fibrosis, and adipocyte-driven functionalization. Extracellular matrix (ECM) hydrogels have demonstrated utility in tissue regeneration, and decreasing inflammation and fibrosis in various tissues. Therefore, we hypothesized that a Decellularized Porcine Dermal (DPD) hydrogel to support ADM integration would prevent excessive fibrosis, regulate the macrophage response, and promote adipogenesis. Exploration of DPD hydrogel during ADM implantation in mice (healthy and radiated) revealed long-term effects of irradiation on implant wound healing. DPD hydrogel rescued radiation-induced fibrosis, restoring capsule thickness of healthy mice, and did not increase the fibroblast migration into the ADM. As a modulating soft tissue filler, DPD hydrogel also promoted adipocyte infiltration in healthy and irradiated mice. Detailed macrophage analysis showed that radiation led to the increase in pro-inflammatory, transition, and reparative markers. Despite relatively subtle effects on individual macrophage phenotype markers, multidimensional flow cytometry analysis revealed that DPD hydrogel temporally regulated two subpopulations. he presence of DPD resulted in significantly reduced CD9<sup>Hi</sup>Arg1<sup>Hi</sup>CD301b<sup>Lo</sup> and CD163<sup>Hi</sup>CD38<sup>Hi</sup>CD301b<sup>Hi</sup> macrophages in healthy mice at one week, and a significant increase in CD9<sup>High</sup> macrophages with low expression of other markers at 6 weeks in irradiated mice. DPD hydrogel promotes a decreased fibrotic, and adipocyte-promoting coordination of wound healing in healthy and irradiated wound beds while not disrupting the immunomodulatory effects of ADM.</div></div><div><h3>Statement of significance</h3><div>Acellular Dermal Matrix (ADM) provides mechanical and soft tissue support in post-mastectomy implant-based breast reconstruction, and positively affects wound healing. Following breast reconstruction, skin flap necrosis, edema, and previous radiation therapy can hinder ADM integration. Effective wound healing and biomaterial integration requires regulating the cellular immune response. Extracellular matrix hydrogels have demonstrated utility in tissue regeneration and decreasing inflammation and fibrosis in various tissues, but has yet to be utilized in the setting of breast reconstruction. Here, we demonstrated that a decellularized dermal hydrogel as an adjunct to ADM, decreases fibrosis and promotes adipogenesis during the coordination of wound healing in healthy and clinically relevant microenvironments that have received radiation therapy while not disrupting the immunomodulatory effects of implanted ADM.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"191 ","pages":"Pages 260-275"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634125","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}
引用次数: 0
In vitro corrosion and biocompatibility of additively manufactured biodegradable molybdenum 添加剂制造的可生物降解钼的体外腐蚀性和生物相容性。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.019
Zhipei Tong , Gencheng Gong , He Huang , Guixing Cai , Liudang Fang , Hui Yu , Chuanqiang Li , Yufeng Zheng , Dong Bian
Recently, molybdenum (Mo) has been recognized a promising biodegradable metal, however, it is difficult to be processed through traditional deformation or machining due to its high strength & hardness. Additive manufacturing is a good way to get rid of this dilemma. Here, Mo components were directly fabricated with fine Mo powder through selective laser melting (SLM). Microstructure, in-vitro corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through rotary swaging (RS), ineluctable hot cracks were found in SLMed bulk Mo, and those defects accelerated the initial ion release rate (1.31 μg·mL−1·d−1 during the first week, one order of magnitude higher than that of RSed Mo). The unique SLMed microstructure resulted in different surface chemical components, constituent phases and corrosion layer structures, thus leading to a different corrosion mode and corrosion evolution along with time. SLMed Mo exhibited good hemocompatibility, and mouse/rat-derived mesenchymal stem cells have certain tolerance to soluble Mo in the sample extracts. However, the deteriorative surface condition on SLMed Mo impaired its biocompatibility to directly attached cells. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Additive manufacturing is a powerful tool to fabricate Mo based structural parts, however, the issue of microstructural defects should be well resolved. Close attention should be paid to the hot-cracks and accompanied fast & non-uniform corrosion.

Statement of Significance

Additive manufacturing is a good way to fabricate implants based on refractory and un-processable biodegradable metals. Here, Mo components were directly fabricated with Mo powder through selective laser melting (SLM). Microstructure, in-vitro corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through traditional rotary swaging (RS), the unique SLMed microstructure resulted in different corrosion mode and corrosion evolution along with time. Localized corrosion appeared at the micro-cracks in SLMed samples, thus leading to a 10-fold ion release at week 1. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Close attention should be paid to the hot-cracks and accompanied fast & non-uniform corrosion.
近来,钼(Mo)被认为是一种前景广阔的可生物降解金属,但由于其强度和硬度较高,很难通过传统的变形或机械加工进行加工。增材制造是解决这一难题的好方法。在这里,我们通过选择性激光熔化(SLM)技术,用细钼粉直接制造钼部件。研究人员对获得的钼的微观结构、体外腐蚀行为和生物相容性进行了深入研究。与通过旋转锻造(RS)制造的钼相比,在 SLMed 块状钼中发现了不可避免的热裂纹,这些缺陷加速了初始离子释放率(第一周为 1.31 μg-mL-1-d-1,比 RSed 钼高一个数量级)。独特的 SLMed 显微结构导致了不同的表面化学成分、组成相和腐蚀层结构,从而导致了不同的腐蚀模式和腐蚀随时间的演变。SLMed Mo 具有良好的血液相容性,小鼠/大鼠间充质干细胞对样品提取物中的可溶性 Mo 有一定的耐受性。然而,SLMed Mo 的表面状况恶化,影响了它对直接附着细胞的生物相容性。细胞可以附着在 SLMed Mo 上,但它们的增殖和扩散会受到影响,并进一步受到腐蚀。增材制造是制造钼基结构件的有力工具,但应妥善解决微结构缺陷问题。应密切关注热裂纹以及伴随而来的快速和不均匀腐蚀。意义说明:增材制造是制造基于难熔和不可加工生物降解金属的植入物的好方法。在这里,我们通过选择性激光熔化(SLM)技术直接用钼粉末制造钼部件。研究人员对获得的钼的微观结构、体外腐蚀行为和生物相容性进行了深入研究。与通过传统的旋转锻造(RS)工艺制作的钼相比,独特的 SLMed 显微结构导致了不同的腐蚀模式和腐蚀随时间的变化。在 SLMed 样品的微裂缝处出现了局部腐蚀,因此在第 1 周时离子释放量增加了 10 倍。细胞可以附着在 SLMed Mo 上,但它们的增殖和扩散会随着进一步的腐蚀而受到影响。应密切关注热裂纹以及伴随的快速和不均匀腐蚀。
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引用次数: 0
Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation 构建压电、导电和可注射水凝胶,通过电刺激促进伤口愈合。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.028
Yunyun Wu , Yanjing Wang , Weili Li , Diyi Li , Panpan Song , Yaqing Kang , Xiaoqing Han , Xinbo Wang , Hongkun Tian , Abdur Rauf , Jiao Yan , Haiyuan Zhang , Xi Li
Piezoelectric, conductive, and injectable hydrogel (SPG hydrogel) is constructed to rapidly close wounds, efficiently harvest biomechanical energy from animal motion, and generate electrical stimulation for electrotherapy of wound healing. 3-amino-4-methoxybenzoic acid (AMB) monomer was polymerized and grafted onto the gelatin, which was further crosslinked using EDC/NHS and embedded with strontium titanate nanoparticles (80.5 wt%), forming SPG hydrogel. This SPG hydrogel had high tissue adhesion ability, and could generate the output voltage (maximum output voltage 1 V) and current (maximum output current 0.5 nA) upon mechanical bending, promoting NIH-3T3 cell migration and proliferation. Upon application to the mice wound model, the SPG hydrogel rapidly closed the skin wound, smoothed the wound's appearance, reduced the remaining wound size, and increased epidermal thickness, demonstrating remarkable wound healing capabilities. This study suggests that the body motion-promoted electrotherapy offers a promising strategy for wound healing.

Statement of significance

Piezoelectric nanomaterials are often incorporated into hydrogels to create piezoelectric hydrogels for wound healing. However, piezoelectric nanomaterials tend to agglomerate within the hydrogel matrix, and the hydrogel's low conductivity hinders efficient electron transfer. Together, both factors significantly reduce the piezoelectric effect. In this study, we developed an SPG hydrogel to improve the homogeneity and conductivity of the piezoelectric hydrogel. We first designed a conductive PG hydrogel and then immoblized piezoelectric STO nanoparticles within its matrix through coordination chemistry. Upon mechanical deformation, the uniformly distributed STO nanoparticles can generate electricity, which can efficiently transfer through the conductive matrix to the hydrogel's surface. This design shows great potential for wound healing applications.
压电、导电和可注射水凝胶(SPG 水凝胶)的构造可快速闭合伤口,从动物运动中有效采集生物力学能量,并产生电刺激用于伤口愈合电疗。将 3-氨基-4-甲氧基苯甲酸(AMB)单体聚合并接枝到明胶上,然后使用 EDC/NHS 进一步交联,并嵌入钛酸锶纳米颗粒(80.5 wt%),形成 SPG 水凝胶。这种 SPG 水凝胶具有很强的组织粘附能力,在机械弯曲时能产生输出电压(最大输出电压为 1 V)和电流(最大输出电流为 0.5 nA),促进 NIH-3T3 细胞迁移和增殖。在小鼠伤口模型上应用 SPG 水凝胶后,皮肤伤口迅速闭合,伤口外观平滑,剩余伤口面积缩小,表皮厚度增加,显示出显著的伤口愈合能力。这项研究表明,人体运动促进电疗法为伤口愈合提供了一种前景广阔的策略。意义说明:压电纳米材料通常被加入水凝胶中,形成用于伤口愈合的压电水凝胶。然而,压电纳米材料容易在水凝胶基质中聚集,而且水凝胶的低导电性阻碍了电子的有效传输。这两个因素加在一起,大大降低了压电效应。在本研究中,我们开发了一种 SPG 水凝胶,以提高压电水凝胶的均匀性和导电性。我们首先设计了一种导电 PG 水凝胶,然后通过配位化学将压电 STO 纳米粒子固定在其基质中。在机械变形时,均匀分布的 STO 纳米粒子可以产生电能,电能可以通过导电基质有效地传递到水凝胶表面。这种设计在伤口愈合方面具有巨大的应用潜力。
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引用次数: 0
Multi-phoretic nanomotor with consistent motion direction for enhanced cancer therapy 具有一致运动方向的多流体纳米马达,用于增强癌症治疗。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-01 DOI: 10.1016/j.actbio.2024.11.037
Wei Zhang , Yangyang Xiang , Qi Guo , Xiaotong Wang , Lukai Zhang , Jiaxin Guo , Ridong Cong , Wei Yu , Xing-Jie Liang , Jinchao Zhang , Dandan Liu
Nanomotors have emerged as promising candidates for the deep penetration of loaded drugs into cancer stem cells (CSCs) located within the core of tumor tissues. A crucial factor in maximizing the clinical potential of nanomotors lies in their ability to respond dynamically to various stimuli in the tumor microenvironment. By adjusting their propulsion mechanisms in response to various stimuli, nanomotors can maintain directional movement, thus improving drug distribution and therapeutic efficacy. In this study, we present the design of a pH-responsive multi-phoretic propelled Janus nanomotor, comprising a SiO2@Pt core@shell nanosphere and half-wrapped acrylic acid polymers (PAA)-conjugated gold (Au) nanoparticles (JMSNs@Pt@P-Au). The JMSNs@Pt@P-Au catalyze endogenous H2O2 into O2, propelling the nanomotors into solid tumors. Within the tumor microenvironment, the contraction of PAA triggers contact between the Au and Pt layers, facilitating self-electrophoresis propulsion. Simultaneously, a local thermal gradient is generated on the Au layer under near-infrared light irradiation, propelling the nanomotor through thermophoresis. Exploiting the unique structure of JMSNs@Pt@P-Au, the driving forces generated by H2O2 catalysis, self-electrophoresis, and thermophoresis exhibit consistent motion directions. This consistency not only provides thrust for deep penetration but also enhances their targeted therapeutic efficiency against CSCs in vivo. This combination of nanomotor-driven power sources holds significant potential for designing intelligent, active drug delivery systems for effective CSC-targeted cancer therapy.

Statement of Significance

Deep penetration of nanomedicine in solid tumor tissue and cells is still an important challenge that restricts the therapeutic effect. Multiple-propelled nanomotors have been confirmed to be self-propulsive that overcome the limited penetration in solid tumor. However, their effective translation toward clinical applications is limited due to the inability to alter their propelled mechanisms in response to the actual physiological environment, resulting in speed and inconsistent movement directions. In this work, we designed a multi-phoretic propelled Janus nanomotor (JMSNs@Pt@P-Au) that exhibited three propelled mechanisms in response to the changes of pH value. Noteworthy is their heightened speed and remarkable tumor tissue penetration observed in vitro and in vivo without adverse effects. Such multi-phoretic propulsion offers considerable promise for developing advanced nanomachines with a stimuli-responsive switch of propulsion modes in biomedical applications.
纳米马达已成为将负载药物深入渗透到位于肿瘤组织核心的癌症干细胞(CSCs)的有前途的候选药物。要最大限度地发挥纳米马达的临床潜力,关键因素在于它们能够对肿瘤微环境中的各种刺激做出动态响应。通过调整其推进机制以应对各种刺激,纳米马达可以保持定向运动,从而改善药物分布和疗效。在本研究中,我们设计了一种 pH 响应型多蠕动推进 Janus 纳米马达,它由 SiO2@Pt 核@壳纳米球和半包裹的丙烯酸聚合物(PAA)-共轭金(Au)纳米粒子(JMSNs@Pt@P-Au)组成。JMSNs@Pt@P-Au 可将内源性 H2O2 催化成 O2,从而将纳米马达推进实体瘤。在肿瘤微环境中,PAA 的收缩会触发金层和铂层之间的接触,从而促进自电泳推进。同时,在近红外线照射下,金层上会产生局部热梯度,通过热泳推动纳米马达。利用 JMSNs@Pt@P-Au 的独特结构,H2O2 催化、自电泳和热泳产生的驱动力表现出一致的运动方向。这种一致性不仅为深层渗透提供了推力,还提高了它们在体内对 CSCs 的靶向治疗效率。这种纳米电机驱动动力源的组合为设计智能活性给药系统提供了巨大潜力,可用于有效的 CSC 靶向癌症治疗。意义声明:纳米药物在实体瘤组织和细胞中的深层渗透仍然是限制治疗效果的一个重要挑战。多推进纳米电机已被证实具有自推进能力,可以克服在实体瘤中的有限穿透性。然而,由于无法根据实际生理环境改变其推进机制,导致其运动速度和运动方向不一致,从而限制了其在临床应用中的有效转化。在这项工作中,我们设计了一种多蠕动推进的 Janus 纳米马达(JMSNs@Pt@P-Au),它能根据 pH 值的变化表现出三种推进机制。值得注意的是,在体外和体内观察到它们的速度更快,对肿瘤组织的穿透力更强,且无不良影响。这种多蠕动推进方式为开发具有刺激响应式推进模式切换的先进纳米机械在生物医学领域的应用提供了广阔前景。
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Acta Biomaterialia
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