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Advances in Pulmonary Protein Delivery Systems 肺蛋白输送系统的进展
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-03-08 DOI: 10.1002/anbr.202300176
Yuanyuan Zhao, Shuai Liu, Xueguang Lu

Protein-based therapeutics and vaccines play a pivotal role in the realm of biomedical science. Pulmonary administration offers several advantages including rapid adsorption, non-invasive, increased local drug concentration, and bypassed first-pass metabolism, thus holding great potential to address multiple unmet medical needs in lung-related diseases and vaccination. However, the limited success of inhaled proteins in clinical settings highlights the challenges associated with protein stability and the physiological barriers within the respiratory system. To overcome these hurdles, a variety of delivery systems including polymers, liposomes, cell-derived membranes, and inorganic materials are developed to improve the stability, mucus penetration, retention time, and bioavailability of proteins. With the outbreak of COVID-19, the pulmonary administration of proteins has drawn great attention. In this review, the design principle, preparation, biomedical application, progress in clinical translation, advantages, and disadvantages of each kind of delivery system are summarized, with an emphasis on carrier materials.

基于蛋白质的疗法和疫苗在生物医学领域发挥着举足轻重的作用。肺部给药具有快速吸附、非侵入性、提高局部药物浓度和绕过首过代谢等优势,因此在解决肺部相关疾病和疫苗接种等多种未满足的医疗需求方面具有巨大潜力。然而,吸入蛋白质在临床应用中取得的成功有限,这凸显了与蛋白质稳定性和呼吸系统内生理屏障相关的挑战。为了克服这些障碍,人们开发了各种给药系统,包括聚合物、脂质体、细胞衍生膜和无机材料,以提高蛋白质的稳定性、粘液渗透性、保留时间和生物利用率。随着 COVID-19 的爆发,蛋白质的肺部给药引起了极大关注。本综述总结了各种给药系统的设计原理、制备方法、生物医学应用、临床转化进展、优缺点,重点介绍了载体材料。
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引用次数: 0
Monitoring the Intracellular Fate of Molecular Beacons: The Challenge of False Positive Signals 监测分子信标的细胞内命运:假阳性信号的挑战
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-03-08 DOI: 10.1002/anbr.202300147
Diogo Volpati, Pedro H. B. Aoki, Therese B. Johansson, Roberto Munita, Frida Ekstrand, Sabrina Ruhrmann, Karl Bacos, Charlotte Ling, Christelle N. Prinz

Molecular beacons (MBs) have been used on surfaces for detecting oligonucleotides. Attempts to use them intracellularly for monitoring mRNA content have been made, however, without any clear conclusion regarding the reliability of the method, mainly due to false positive signals. To reach an understanding of the intracellular fate of MBs, a critical question remains: how long after MB delivery and where in the cell does a false positive signal appear? To answer that question, the MB delivery method should allow for a time-stamped synchronized delivery of MBs to multiple cells, resulting in MBs being distributed in the cytosol immediately after delivery. Herein, nanostraws are used to inject MBs targeting insulin (Ins1) mRNA directly in the cytosol of clonal beta-cells, and the evolution of the MB fluorescence in time and space is monitored. The results show an MB translocation to the nucleus, where MBs are degraded or where they open nonspecifically, before the fluorophore alone is expelled back from the nucleus to the cytosol. The signal translocation to the nucleus and back to the cytosol is faster when scrambled MBs are used. The results shed light on the intracellular fate of MBs and highlight the short time scales before false positive signals become predominant.

分子信标(MBs)已被用于表面检测寡核苷酸。不过,人们曾尝试在细胞内使用它们来监测 mRNA 含量,但对该方法的可靠性没有得出明确结论,主要原因是出现了假阳性信号。要想了解甲基溴在细胞内的去向,一个关键问题仍然存在:甲基溴递送后多长时间,在细胞的哪个部位会出现假阳性信号?要回答这个问题,甲基溴递送方法应允许将甲基溴同步递送到多个细胞,从而使甲基溴在递送后立即分布在细胞质中。在这里,使用纳米吸盘将靶向胰岛素(Ins1)mRNA的甲基溴直接注入克隆β细胞的细胞质,并监测甲基溴荧光在时间和空间上的演变。结果表明,在荧光团单独从细胞核排回细胞质之前,MB 易位到细胞核,在那里 MB 被降解或非特异性开放。使用加扰甲基溴时,信号转运到细胞核再返回细胞质的速度更快。这些结果揭示了甲基溴在细胞内的命运,并强调了假阳性信号占主导地位之前的短时间尺度。
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引用次数: 0
Nanomedicine-Enabled Mild Photothermal Therapy Strategies for Enhanced Antitumor Treatment 增强抗肿瘤治疗的纳米药物温和光热疗法策略
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-03-07 DOI: 10.1002/anbr.202470031
Yongjuan Li, Xinran Zhu, Ya Dong, Yang Yang, Danyang Shen, Zhenzhen Li, Rui Li, Xiaowei Dang, Zhihai Qin, Kelong Fan

Photothermal Therapy

Mild photothermal therapy (mPTT, <45 °C) has garnered considerable attention in antitumor therapy, despite the thermal resistance induced by heat shock proteins. In article 2300094, Kelong Fan and co-workers discuss the current landscape of photothermal agents, elucidate the underlying mechanisms of mPTT, highlight the benefits of mPTT in combination therapy, and explore the potential of nanomedicines to enhance mPTT efficacy.

光热疗法 轻度光热疗法(mPTT,45 °C)在抗肿瘤治疗中备受关注,尽管热休克蛋白会引起热阻。在第 2300094 号文章中,Kelong Fan 及其合作者讨论了光热疗法的现状,阐明了温和光热疗法的基本机制,强调了温和光热疗法在联合治疗中的优势,并探讨了纳米药物提高温和光热疗法疗效的潜力。
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引用次数: 0
Advances of Structural Design and Biomedical Applications of Tobacco Mosaic Virus Coat Protein 烟草花叶病毒外壳蛋白的结构设计和生物医学应用进展
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-03-07 DOI: 10.1002/anbr.202300135
Jialun Zhang, Haobo He, Fanmeng Zeng, Mingming Du, Dehua Huang, Guangcun Chen, Qiangbin Wang

Recognized as the primary RNA virus to be categorized and extensively studied, the tobacco mosaic virus (TMV) is foundational to advancements in virology, molecular biology, and biomaterials. Over the past few decades, the deep comprehension of the TMV coat protein (TMVcp) molecular structure and assembly principles has stimulated a surge in research on TMVcp structural design using genetic engineering and chemical modification techniques. The unique characteristics of TMVcp, including its nanoscale orderly structure, ease of modification, and considerable drug loading capacity, have enabled significant progress in its biomedical applications. This review summarizes the advanced strategies deployed for TMVcp design and multidimensional assembly and underscores the prototypical applications of TMVcp-based biomaterials in bioimaging, drug delivery, tissue engineering, and biosensing. Ultimately, the future prospects of TMVcp research in structural design and biomedical applications are explored, which encompass artificial intelligence-guided structural and functional design, the development of stimulus-responsive biomaterials, and potential clinical translation.

烟草花叶病毒(TMV)被认为是最早被分类和广泛研究的 RNA 病毒,对病毒学、分子生物学和生物材料的发展具有奠基性意义。过去几十年来,随着对烟草花叶病毒衣壳蛋白(TMVcp)分子结构和组装原理的深入理解,利用基因工程和化学修饰技术进行 TMVcp 结构设计的研究激增。TMVcp 的独特特性,包括纳米级有序结构、易于修饰和可观的药物负载能力,使其在生物医学应用方面取得了重大进展。本综述总结了 TMVcp 设计和多维组装的先进策略,并强调了基于 TMVcp 的生物材料在生物成像、药物输送、组织工程和生物传感方面的典型应用。最后,还探讨了 TMVcp 研究在结构设计和生物医学应用方面的未来前景,其中包括人工智能指导的结构和功能设计、刺激响应型生物材料的开发以及潜在的临床转化。
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引用次数: 0
Cutting-Edge Achievements of Inner Ear Drug Delivery Systems 内耳给药系统的尖端成果
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-03-01 DOI: 10.1002/anbr.202400004
Hui Zhang, Dongyu Xu, Huan Wang, Renjie Chai, Yuanjin Zhao

The intricate physiological structure of the inner ear presents challenges for traditional medication treatment strategies, including systemic adverse responses, trouble penetrating the blood–labyrinth barrier, and low local cochlear concentration, resulting in poor therapeutic outcomes. An intriguing tactic that is extensively developed over decades is utilizing drug delivery systems to transport medication molecules to the inner ear. Herein, the challenges associated with inner ear delivery are discussed, cutting-edge achievements in inner ear drug delivery systems are emphasized, including nano-, micro-, and macrocarriers, and finally opportunities to leverage advanced technologies to improve existing drug delivery strategies are highlighted.

内耳错综复杂的生理结构给传统的药物治疗策略带来了挑战,包括全身不良反应、难以穿透血-迷宫屏障以及局部耳蜗浓度低等,从而导致治疗效果不佳。经过数十年的广泛开发,一种令人感兴趣的方法是利用药物输送系统将药物分子输送到内耳。本文讨论了与内耳给药相关的挑战,强调了内耳给药系统的前沿成就,包括纳米、微米和大载体,最后强调了利用先进技术改进现有给药策略的机会。
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引用次数: 0
Natural Polymer-Based Materials for Wound Healing Applications 用于伤口愈合的天然聚合物基材料
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-02-22 DOI: 10.1002/anbr.202300131
Trinh Thi-Phuong Ho, Hien A. Tran, Vinh Khanh Doan, Joanneke Maitz, Zhe Li, Steven G. Wise, Khoon S. Lim, Jelena Rnjak-Kovacina

Skin injuries pose significant health challenges, with conditions like burns and diabetic, venous, and pressure ulcers presenting complex wound management scenarios. Effective wound care strategies for these injuries encompass a range of interventions, from simple wound dressings to bioactive materials and surgical procedures involving skin substitutes and skin grafting. This review explores the potential of natural polymers, including silk, collagen, gelatin, elastin, cellulose, chitosan, alginate, and hyaluronic acid, in wound management. Natural polymers offer several advantages, including abundance, biodegradability, and compatibility with traditional and modern material fabrication techniques, and have demonstrated safety and efficacy in clinical applications, modulating various facets of the wound healing process. Highlighting preclinical and clinical studies, along with commercial products, this review showcases the versatility and utility of natural polymers in wound management and provides insights into emerging developments, such as 3D bioprinting and stimuli-responsive materials, which hold promise for personalized wound treatments. Additionally, we discuss the importance of the material format and morphology in engineering the next generation of wound dressings and skin substitutes, offering a pathway to optimize natural polymers for enhanced wound healing outcomes.

皮肤损伤给人们的健康带来了巨大挑战,烧伤、糖尿病、静脉溃疡和压迫性溃疡等疾病都会带来复杂的伤口管理问题。针对这些创伤的有效伤口护理策略包括一系列干预措施,从简单的伤口敷料到生物活性材料以及涉及皮肤替代品和皮肤移植的外科手术。本综述探讨了天然聚合物(包括蚕丝、胶原蛋白、明胶、弹性蛋白、纤维素、壳聚糖、海藻酸和透明质酸)在伤口护理方面的潜力。天然聚合物具有多种优势,包括丰富性、生物降解性以及与传统和现代材料制造技术的兼容性,并已在临床应用中证明了其安全性和有效性,可调节伤口愈合过程的各个方面。本综述重点介绍了临床前和临床研究以及商业产品,展示了天然聚合物在伤口管理中的多功能性和实用性,并深入探讨了三维生物打印和刺激响应材料等新兴发展,这些技术为个性化伤口治疗带来了希望。此外,我们还讨论了材料形式和形态在下一代伤口敷料和皮肤替代品工程中的重要性,为优化天然聚合物以提高伤口愈合效果提供了途径。
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引用次数: 0
Advances and Challenges in Cerebral Organoids Research 脑有机体研究的进展与挑战
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-02-17 DOI: 10.1002/anbr.202300126
Dandan Luo, Jiaqi Xu, Fuyao Liu, Zhen Gu

Cerebral organoids are three-dimensional (3D) aggregates with a more advanced composition, maturation, and architecture. It has emerged as a novel and sophisticated model system for studying neurodevelopment and neurological disorders, in comparison to conventional two-dimensional (2D) cell cultures. However, due to the extraordinarily complex nature of brain development, current cerebral organoids are not as functional and mature as brains. The development of cerebral organoids requires a culture system with sufficient developmental patterning factors, essential cell components, and vasculature. In this review, the critical factors and events that contribute to the development of cerebral organoids are focused on. The advanced design, fabrication techniques, and technologies are also discussed to enhance the application potential of cerebral organoid technology.

脑器质性细胞是一种三维(3D)聚集体,具有更先进的组成、成熟度和结构。与传统的二维(2D)细胞培养相比,它已成为研究神经发育和神经系统疾病的一种新颖而复杂的模型系统。然而,由于大脑发育的性质异常复杂,目前的脑器官组织并不像大脑那样具有功能性和成熟性。脑器官组织的发育需要一个具有足够的发育模式因子、基本细胞组分和血管的培养系统。在这篇综述中,我们将重点讨论有助于脑器官组织发育的关键因素和事件。此外,还讨论了先进的设计、制造技术和工艺,以提高大脑类器官技术的应用潜力。
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引用次数: 0
Dendrimer-Based Nanodrugs for Chemodynamic Therapy of Tumors 用于肿瘤化学动力疗法的树枝状聚合物纳米药物
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-02-17 DOI: 10.1002/anbr.202300149
Caiyun Zhang, Yunqi Guo, Mingwu Shen, Xiangyang Shi

To realize precise tumor treatment, chemodynamic therapy (CDT) that utilizes metal element to trigger Fenton or Fenton-like reaction to generate cytotoxic hydroxyl radicals in tumor region has been widely investigated. Recently, the dendrimers featured with abundant surface functional groups and excellent biocompatibility are regarded as promising carriers of metal elements for tumor delivery. Much effort has been devoted to design dendrimer-based nanodrugs for CDT and CDT-involved synergistic therapy of tumors. Herein, the recent advances in the construction of dendrimer-based nanodrugs (in most cases, poly(amidoamine) dendrimers) for CDT, CDT/chemotherapy, CDT/phototherapy, CDT/gene therapy, or CDT-involved multimodal therapy are reviewed. Furthermore, the future perspectives with regard to the development of dendrimer-based nanodrugs for CDT-involved tumor treatment are also briefly discussed.

为实现肿瘤的精准治疗,利用金属元素引发芬顿或类芬顿反应,从而在肿瘤区域产生具有细胞毒性的羟基自由基的化学动力学疗法(CDT)已被广泛研究。最近,具有丰富表面官能团和良好生物相容性的树枝状聚合物被认为是很有前景的肿瘤金属元素递送载体。人们致力于设计基于树枝状聚合物的纳米药物,用于 CDT 和 CDT 参与的肿瘤协同治疗。本文综述了最近在构建用于 CDT、CDT/化疗、CDT/光疗、CDT/基因治疗或 CDT 参与的多模式治疗的树枝状聚合物基纳米药物(大多数情况下为聚(氨基胺)树枝状聚合物)方面取得的进展。此外,还简要讨论了开发用于 CDT 相关肿瘤治疗的树枝状聚合物纳米药物的未来前景。
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引用次数: 0
Versatile Platforms of Microneedle Patches Loaded with Responsive Nanoparticles: Synthesis and Promising Biomedical Applications 装载响应性纳米粒子的微针贴片的多功能平台:合成与前景广阔的生物医学应用
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-02-15 DOI: 10.1002/anbr.202300142
Rixin Xie, Wenjing Li, Kexin Shi, Li Yang, Hongzhong Chen, Shaoyun Jiang, Xiaowei Zeng

Microneedle array systems loaded with responsive nanoparticles have received increasing attention due to the advantages of good drug stability, targeting ability, controlled release of drugs, high bioavailability, painlessness, and good patient compliance. Compared with oral drug delivery, microneedle transdermal drug delivery eliminates the need to pass through the gastrointestinal tract and liver, reducing the metabolic consumption of drugs by first-pass effect. While compared with intravenous drug delivery, microneedle transdermal drug delivery reduces patient discomfort and does not require professional administration. However, there are few review articles on microneedles loaded with responsive nanoparticles. Herein, the current researches on microneedles loaded with specific responsive nanoparticles such as glucose-responsive, pH-responsive, enzyme-responsive, light-responsive, magnetic-responsive, ultrasound-responsive, and multiresponsive, and the biomedical application of these microneedle array systems are summarized. In addition, the challenges and prospects of microneedle strategies loaded with responsive nanoparticles are briefly discussed, which will facilitate the development of such versatile drug-delivery strategy.

由于具有药物稳定性好、靶向性强、药物释放可控、生物利用度高、无痛苦、患者依从性好等优点,负载有响应性纳米颗粒的微针阵列系统受到越来越多的关注。与口服给药相比,微针透皮给药无需经过胃肠道和肝脏,通过首过效应减少了药物的代谢消耗。与静脉给药相比,微针透皮给药可减少患者的不适感,且无需专业人员给药。然而,关于微针载入响应性纳米颗粒的综述文章却很少。本文总结了负载特定响应性纳米粒子(如葡萄糖响应性、pH响应性、酶响应性、光响应性、磁响应性、超声响应性和多响应性)的微针的研究现状,以及这些微针阵列系统在生物医学方面的应用。此外,还简要讨论了负载响应性纳米粒子的微针策略所面临的挑战和前景,这将促进这种多功能给药策略的发展。
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引用次数: 0
The Cutting-Edge Progress in Covalent Organic Framework-Based Nanomedicine 共价有机框架纳米医学的前沿进展
IF 3.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-02-08 DOI: 10.1002/anbr.202300163
Huaijuan Guo, Yang Liu, Chao Fang, Xuebing Yan, Kun Zhang, Huali Gao

Covalent organic frameworks (COFs) are a class of porous crystalline materials with exceptional properties, constructed through covalently linked organic units. COFs are extensively applied in the field of biomedicine, particularly in the context of anticancer treatments. First, this review summarizes the diverse synthetic methods of COFs, including solvothermal synthesis, microwave-assisted synthesis, room temperature synthesis, interface synthesis, ionothermal techniques, mechanical grinding, and electrochemical methods, and their impacts on the material's structure and performance. Second, COFs exhibit tremendous potential in the field of cancer therapy because of their orderly lattice structure, tunable pore sizes, high surface area, and excellent thermal and chemical stability. Therefore, the article deeply explores the applications of COFs in diverse cancer treatment modalities, encompassing early diagnostic bioimaging, drug delivery, various phototherapies, chemodynamic therapy, sonodynamic therapy, radiation therapy, and their combined therapeutic strategies. Finally, the article points out current research challenges and future directions in this field.

共价有机框架(COFs)是一类多孔晶体材料,通过共价连接的有机单元构建而成,具有优异的性能。COFs 被广泛应用于生物医学领域,尤其是抗癌治疗方面。首先,本综述总结了 COFs 的多种合成方法,包括溶热合成、微波辅助合成、室温合成、界面合成、离子热技术、机械研磨和电化学方法,以及这些方法对材料结构和性能的影响。其次,COF 因其有序的晶格结构、可调的孔径、高比表面积以及优异的热稳定性和化学稳定性,在癌症治疗领域展现出巨大的潜力。因此,文章深入探讨了 COFs 在多种癌症治疗模式中的应用,包括早期生物成像诊断、药物输送、各种光疗法、化学动力疗法、声动力疗法、放射疗法及其联合治疗策略。最后,文章指出了这一领域当前面临的研究挑战和未来发展方向。
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引用次数: 0
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Advanced Nanobiomed Research
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