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Current situation and challenges of polyhydroxyalkanoates-derived nanocarriers for cancer therapy 用于癌症治疗的聚羟基烷酸酯纳米载体的现状与挑战
Q1 Engineering Pub Date : 2024-10-30 DOI: 10.1016/j.smaim.2024.10.004
Xiao-Yun Huang , Zheng-Dong Qi , Jin-Wei Dao , Dai-Xu Wei
The sustained-release system for chemotherapeutic drugs or photosensitizer based on drug-loaded biopolyester nanocarriers can effectively reduce the overall dosage and frequency of administration, thereby mitigating side effects such as immunosuppression and drug resistance caused by prolonged chemotherapy. Compared to polylactic acid (PLA), microorganism-derived polyhydroxyalkanoates (PHAs) exhibits superior biocompatibility and more flexible drug release behavior due to their diverse monomer compositions, slower degradation behavior, and milder acidic degradation products, 3-hydroxybutyric acid (3HB). It explains PHAs are more suitable carriers for chemotherapeutic drugs. In this review, we summarize the current situation of PHA-derived nanocarriers (PHA-NCs) for cancer therapy, including the advantages, preparation methods, and anticancer applications. Furthermore, we also analyzed the current limitations in the application of PHA-NCs for cancer therapy and proposed existing challenges along with strategies for future development. With the rapid advancements in synthetic biology and nanomedicine, we believe that PHA will once again attract significant attention.
基于载药生物聚酯纳米载体的化疗药物或光敏剂缓释系统可有效减少总体剂量和给药频率,从而减轻长期化疗引起的免疫抑制和耐药性等副作用。与聚乳酸(PLA)相比,微生物衍生的聚羟基烷酸酯(PHA)因其单体成分多样、降解行为缓慢、降解产物 3-hydroxybutyric acid(3HB)酸性较弱等特点,具有更优越的生物相容性和更灵活的药物释放行为。这说明 PHAs 更适合作为化疗药物的载体。在这篇综述中,我们总结了PHA衍生纳米载体(PHA-NCs)用于癌症治疗的现状,包括其优势、制备方法和抗癌应用。此外,我们还分析了目前 PHA-NCs 在癌症治疗中应用的局限性,并提出了现有挑战和未来发展策略。随着合成生物学和纳米医学的快速发展,我们相信 PHA 将再次引起人们的广泛关注。
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引用次数: 0
Nanobody-as versatile tool emerging in autoimmune diseases 纳米体--自身免疫性疾病中出现的多功能工具
Q1 Engineering Pub Date : 2024-10-18 DOI: 10.1016/j.smaim.2024.10.003
Ling Wang , Ran Luo , Weilang Zhang , Hanyu Jiang , Yongkang Yu , Wenhu Zhou , Fan Zhang , Jian Ma , Lin Mei
Nanobody (Nb) is derived from the variable domain of heavy-chain antibody (HCAb), naturally displaying notable properties like nano-scale size, exceptional stability, high specificity, low immunogenicity, and cryptic epitope accessibility. These features contribute to its great therapeutic potential as a valuable research tool across diverse diseases, especially autoimmune diseases (AIDs). Caplacizumab (Cablivi®) is the first nanobody drug approved for treating acquired thrombotic thrombocytopenic purpura (aTTP). This review summarizes the biomolecular structure, usage of Nb as a foundation of recombinant constructs, and biochemical properties of nanobodies. As attractive therapeutic candidates, many clinical trials of Nbs have been conducted, elucidating potential therapeutic strategies for AIDs. Therefore, the preclinical development and application of Nbs in AIDs are emphasized throughout this review.
纳米抗体(Nb)源自重链抗体(HCAb)的可变结构域,天然具有纳米级尺寸、超强稳定性、高特异性、低免疫原性和表位隐蔽性等显著特性。这些特性使其具有巨大的治疗潜力,成为各种疾病,尤其是自身免疫性疾病(AIDs)的重要研究工具。卡普拉珠单抗(Cablivi®)是首个获准用于治疗获得性血栓性血小板减少性紫癜(aTTP)的纳米抗体药物。本综述概述了纳米抗体的生物分子结构、作为重组构建物基础的 Nb 的使用以及纳米抗体的生化特性。作为极具吸引力的候选治疗药物,Nbs 已经开展了许多临床试验,阐明了治疗艾滋病的潜在策略。因此,本综述强调了 Nbs 在艾滋病中的临床前开发和应用。
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引用次数: 0
Bioactive MXene hydrogel promotes structural and functional regeneration of skeletal muscle through improving autophagy and muscle innervation 生物活性 MXene 水凝胶通过改善自噬和肌肉神经支配促进骨骼肌的结构和功能再生
Q1 Engineering Pub Date : 2024-10-12 DOI: 10.1016/j.smaim.2024.10.002
Li Zhou , Haixia Zhuang , Xinyu Ye , Wei Yuan , Kai Wang , Donghan Hu , Xiangya Luo , Qiuyu Zhang
Complete skeletal muscle regeneration after traumatic injuries remains a challenge due to impaired regenerative capability and dysregulated microenvironments. Autophagy plays a crucial role in the muscle regeneration process by regulating myogenic and non-myogenic cells. Herein, we report a bioactive MXene hydrogel (FPGM) capable of upregulating autophagy and increasing muscle innervation to restore skeletal muscle structure and function. FPGM possessed excellent electrical conductivity, tissue adhesive ability and antioxidation, which could eliminate excess reactive oxygen species to reduce oxidative stress and decrease the secretion of pro-inflammatory cytokine. FPGM upregulated the autophagy level of myoblasts and promoted the migration and tube formation of endothelial cells as well as myogenic differentiation with negligible toxicity. FPGM accelerated muscle fiber formation and skeletal muscle regeneration by improving autophagy, which could regulate microenvironment through raising M2 macrophages to alleviate excessive inflammation, facilitating angiogenesis and decreasing fibrous scar tissue formation in vivo. Importantly, FPGM could efficiently restore muscle function by improving muscle innervation, tibialis anterior compound muscle action potential amplitude and neuromuscular conduction. This work demonstrates that bioactive MXene hydrogel should be a promising candidate for complete skeletal muscle regeneration.
由于再生能力受损和微环境失调,创伤后骨骼肌的完全再生仍是一项挑战。自噬通过调节成肌细胞和非成肌细胞,在肌肉再生过程中发挥着至关重要的作用。在此,我们报告了一种生物活性 MXene 水凝胶(FPGM),它能够上调自噬并增加肌肉神经支配,从而恢复骨骼肌的结构和功能。FPGM具有良好的导电性、组织粘附性和抗氧化性,能消除过量的活性氧,从而降低氧化应激,减少促炎细胞因子的分泌。FPGM 能提高成肌细胞的自噬水平,促进内皮细胞的迁移和管形成,并促进成肌细胞的分化,其毒性几乎可以忽略不计。FPGM可通过提高自噬水平加速肌纤维的形成和骨骼肌的再生,并可通过提高M2巨噬细胞来调节微环境,从而缓解过度炎症,促进血管生成,减少体内纤维瘢痕组织的形成。重要的是,FPGM 可通过改善肌肉神经支配、胫骨前复合肌动作电位振幅和神经肌肉传导,有效恢复肌肉功能。这项研究表明,生物活性 MXene 水凝胶有望成为骨骼肌完全再生的候选材料。
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引用次数: 0
Progress of smart material in the repair of intervertebral disc degeneration 智能材料在修复椎间盘退变方面的进展
Q1 Engineering Pub Date : 2024-10-09 DOI: 10.1016/j.smaim.2024.10.001
Yisi Liu , Jie Hu , Hao Jiang , Hui He , Liwei Yao , Qianglong Chen , Lijie Wang , Ting Liang , Bin Li , Fengxuan Han
Intervertebral disc degeneration (IVDD) is a prevalent condition leading to back and leg pain as well as chronic disability. It refers to the degeneration of intervertebral disc structure, including the nucleus pulposus, annulus fibrosus, and cartilage endplate. Along with degeneration process, these components can deteriorate, causing pain and functional impairment. To address IVDD, researchers are exploring the use of smart materials as novel therapeutic approaches. This review aims to summarize the application of various stimuli-responsive smart materials (endogenous and exogenous stimuli-responsive materials) in the repair for Intervertebral disc. These smart materials, such as responsive hydrogels, shape-memory polymers, and nanoparticle-based delivery systems, have shown considerable potential in achieving targeted drug delivery and tissue regeneration, and improving clinical outcomes. The ongoing advancement of smart materials towards successful clinical translation holds promise for improving treatment outcomes for IVDD patients, providing more effective and safer therapeutic options.
椎间盘退变(IVDD)是一种导致腰腿痛和慢性残疾的常见疾病。它是指椎间盘结构的退化,包括髓核、纤维环和软骨终板。伴随着退化过程,这些成分会恶化,导致疼痛和功能障碍。为解决 IVDD 问题,研究人员正在探索使用智能材料作为新型治疗方法。本综述旨在总结各种刺激响应智能材料(内源性和外源性刺激响应材料)在椎间盘修复中的应用。这些智能材料,如响应性水凝胶、形状记忆聚合物和基于纳米颗粒的递送系统,在实现定向药物递送和组织再生以及改善临床疗效方面已显示出相当大的潜力。智能材料在临床转化方面的不断进步为改善 IVDD 患者的治疗效果、提供更有效、更安全的治疗方案带来了希望。
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引用次数: 0
Programming-via-spinning: Electrospun shape memory polymer fibers with simultaneous fabrication and programming 通过纺丝编程:同时制造和编程的电纺形状记忆聚合物纤维
Q1 Engineering Pub Date : 2024-09-24 DOI: 10.1016/j.smaim.2024.09.002
Avery Gunderson, Maryam Ramezani, Thalma K. Orado, Mary Beth B. Monroe
Porous shape memory polymer (SMP) scaffolds are promising ‘smart’ materials for potential use in a wide range of biomedical applications. Electrospinning provides an approach to produce fibrous SMP scaffolds to enhance their porosity, mass transfer, and flexibility. Here, we studied the effects of electrospinning parameters (rotating collector rotational speed and solvent) on shape memory and mechanical properties of a biostable thermoplastic polyurethane (PUr) SMP. Scanning electron microscopy confirmed that fiber diameter and tortuosity could be tuned using varied collector rotation speeds and/or solvents. Mechanical properties, including modulus, tensile strength, and ultimate elongation, were tuned independently of chemistry based on variations in fiber architectures. All scaffolds demonstrated shape memory properties. Additionally, due to strains that are trapped in the fibers during the electrospinning process, SMP fibers are programmed into a strained, temporary shape during the fabrication step. These fibers can be immediately triggered to recover to a non-strained primary shape after fabrication to reduce sample preparation time and complexity. As a proof-of-concept, bacterial protease-responsive SMPs were electrospun and exposed to S. aureus in programmed secondary shapes. Upon exposure to bacteria, these SMPs underwent shape recovery, which resulted in reduced bacterial attachment and biofilm formation. These materials could be employed as bacteria-responsive wound dressings in future work. Overall, electrospinning provides a valuable tool for tuning mechanical and shape memory properties independently from chemistry and for programming SMPs during fabrication to enable scale-up of electrospun SMP scaffolds.
多孔形状记忆聚合物(SMP)支架是一种前景广阔的 "智能 "材料,可广泛应用于生物医学领域。电纺丝提供了一种生产纤维状 SMP 支架的方法,以提高其多孔性、传质性和柔韧性。在此,我们研究了电纺丝参数(旋转收集器转速和溶剂)对生物稳定热塑性聚氨酯(PUr)SMP 的形状记忆和机械性能的影响。扫描电子显微镜证实,使用不同的收集器旋转速度和/或溶剂可以调整纤维直径和迂回度。根据纤维结构的变化,机械性能(包括模量、拉伸强度和极限伸长率)的调整与化学性质无关。所有支架都具有形状记忆特性。此外,在电纺丝过程中,由于应变被截留在纤维中,SMP 纤维在制造步骤中被编程为应变的临时形状。制造完成后,可立即触发这些纤维恢复到无应变的初始形状,以减少样品制备时间和复杂性。作为概念验证,细菌蛋白酶响应 SMP 经电纺丝后暴露于金黄色葡萄球菌,形成编程的二级形状。接触细菌后,这些 SMP 会发生形状恢复,从而减少细菌附着和生物膜的形成。在未来的工作中,这些材料可用作细菌响应型伤口敷料。总之,电纺丝提供了一种有价值的工具,可独立于化学反应调整机械和形状记忆特性,并在制造过程中对 SMP 进行编程,从而扩大电纺 SMP 支架的规模。
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引用次数: 0
Ultrasound-activated mechanochemical reactions for controllable biomedical applications 用于可控生物医学应用的超声激活机械化学反应
Q1 Engineering Pub Date : 2024-09-14 DOI: 10.1016/j.smaim.2024.09.001
Maocheng Zuo , Rong Xiao , Fangxue Du , Chong Cheng , Raul D. Rodriguez , Lang Ma , Bihui Zhu , Li Qiu
Intramolecular bonds in small organic molecules, macromolecules, and organic-inorganic hybrids are broken or formed by ultrasound-activated mechanical force that can be applied with spatial and temporal precision for contactless external control of mechanochemical reactions. Ultrasound featuring non-invasiveness, high tissue penetration, and spatiotemporal controllability has shown great potential in controlling the activation of mechanochemical reactions such as chemical bond scission, natural enzyme activation, and catalytic radical generation for targeted drug or gene therapy. Here, we comprehensively summarize the latest research and future trends in ultrasound-activated mechanochemical reactions for smart biomedical applications. First, the mechanism of ultrasound-activated mechanochemical reactions will be outlined. Then, the types of mechanochemical reactions will be carefully discussed. After that, the representative biomedical applications have been summarized from a unique perspective. Finally, we systematically emphasize the current challenges and future outlooks to guide the rational design of ultrasound-activated drug release over conventional drug-loaded therapies. We believe that this review will substantially facilitate the progression and widespread utilization of ultrasound-activated mechanochemical reactions in biomedical applications.
小有机分子、大分子和有机-无机杂化物中的分子内键可通过超声波激活的机械力来断裂或形成,这种机械力可以在空间和时间上精确应用,从而实现对机械化学反应的非接触式外部控制。超声波具有非侵入性、高组织穿透性和时空可控性等特点,在控制化学键断裂、天然酶活化和催化自由基生成等机械化学反应的活化方面显示出巨大的潜力,可用于靶向药物或基因治疗。在此,我们全面总结了超声激活机械化学反应在智能生物医学应用方面的最新研究和未来趋势。首先,我们将概述超声激活机械化学反应的机理。然后,将仔细讨论机械化学反应的类型。然后,从独特的角度总结了具有代表性的生物医学应用。最后,我们系统地强调了当前的挑战和未来的展望,以指导合理设计超声激活药物释放而非传统药物负载疗法。我们相信,这篇综述将极大地推动超声激活机械化学反应在生物医学应用中的发展和广泛应用。
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引用次数: 0
Externally triggered drug delivery systems 外部触发给药系统
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.004
Huiyang Hu , Prabhakar Busa , Yue Zhao , Chao Zhao

Externally triggered drug delivery systems empower patients or healthcare providers to utilize external stimuli to initiate drug release from implanted systems. This approach holds significant potential for clinical disease management, offering appealing features like enhanced patient adherence through the elimination of needles and medication reminders. Additionally, it facilitates personalized medicine by granting patients control over the timing, dosage, and duration of drug release. Moreover, it enables precise drug delivery to targeted locations where external stimuli are applied. Advances in materials science, nanotechnology, chemistry, and biology have been pivotal in driving the development of these systems. This review presents an overview of the progress in research on drug release systems responsive to external stimuli, such as light, ultrasound, magnetic fields, and temperature. It discusses the construction strategies of externally triggered drug delivery systems, the mechanisms governing triggered drug release, and their applications in disease management.

外部触发给药系统使患者或医疗服务提供者能够利用外部刺激来启动植入系统的药物释放。这种方法在临床疾病管理方面具有巨大的潜力,其吸引人的特点包括通过消除针头和用药提醒来提高患者的依从性。此外,它还能让患者控制药物释放的时间、剂量和持续时间,从而促进个性化医疗。此外,它还能将药物精确输送到施加外部刺激的目标位置。材料科学、纳米技术、化学和生物学的进步在推动这些系统的发展方面起到了关键作用。本综述概述了对光、超声波、磁场和温度等外部刺激做出反应的药物释放系统的研究进展。它讨论了外部触发给药系统的构建策略、触发药物释放的机制及其在疾病治疗中的应用。
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引用次数: 0
Magnesium-based bioceramic-enhanced composites fabricated via friction stir processing 通过搅拌摩擦加工制造镁基生物陶瓷增强复合材料
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.006
Matthew S. Dargusch , Nan Yang , Nagasivamuni Balasubramani , Jeffrey Venezuela , Shiyang Liu , Lei Jing , Yu Sen , Jiangtao Qu , Gui Wang , Julie Cairney

Improving the degradation performance and enhancing the biocompatibility are the main challenges of Mg-based biodegradable implants. In this study, a nano-hydroxyapatite-enhanced (nHA) Mg matrix composite was fabricated via friction stir processing and characterised, including microstructure, mechanical, in vitro degradation properties, and cytocompatibility. Hydroxyapatite is renowned for its superior bone compatibility, promoting healing responses and tissue growth. Friction stirring created a gradient grain structure in the alloy, with the stir zone exhibiting the highest grain refinement. The stir zone also contained most of the incorporated nHA and exhibited a strong texture with grains preferentially oriented along the [0001] direction. Immersion and polarisation experiments showed an increase in the FSPed WE43-nHA's corrosion resistance due to the refined microstructure. The treatment also caused a shift in the corrosion mode of the alloy from localized to uniform corrosion despite some localized corrosion associated with the nHA. Cytocompatibility tests in human osteoblast (HOB) cell lines indicated good biocompatibility in the Mg-nHA alloy, with cells exhibiting relatively healthy morphology and increased live cell count. Friction stir processing is a viable manufacturing option for creating Mg-based metal matrix composites with improved corrosion resistance and good biocompatibility.

改善降解性能和提高生物相容性是镁基可生物降解植入物面临的主要挑战。在这项研究中,通过搅拌摩擦加工制造了纳米羟基磷灰石增强(nHA)镁基复合材料,并对其进行了表征,包括微观结构、机械性能、体外降解性能和细胞相容性。羟基磷灰石因其卓越的骨兼容性、促进愈合反应和组织生长而闻名。摩擦搅拌在合金中形成了梯度晶粒结构,搅拌区的晶粒细化程度最高。搅拌区还含有大部分掺入的 nHA,并呈现出强烈的纹理,晶粒优先沿 [0001] 方向取向。浸泡和极化实验表明,由于微观结构的细化,FSPed WE43-nHA 的耐腐蚀性能有所提高。处理还导致合金的腐蚀模式从局部腐蚀转变为均匀腐蚀,尽管 nHA 存在一些局部腐蚀。人类成骨细胞(HOB)细胞系的细胞相容性测试表明,Mg-nHA 合金具有良好的生物相容性,细胞表现出相对健康的形态,活细胞数量增加。搅拌摩擦加工是制造具有更强耐腐蚀性和良好生物相容性的镁基金属基复合材料的可行方法。
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引用次数: 0
Advances of surface modification to alleviate oxidative stress-induced valve degeneration 表面改性在缓解氧化应激引起的瓣膜退化方面取得进展
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.003
Pai Peng , Xinman Hu , Beiduo Wang , Xuelong Wang , Shifen Li , Yongyuan Kang , Xiaofei Dong , Xiayan Yang , Qifeng Yu , Changyou Gao

Valvular heart disease (VHD) is a significant public health threat, with heart valve replacement surgery being the standard treatment for severe cases. Despite of advancements in artificial heart valves, their longevity remains limited due to in vivo degeneration. In consequence, there is an urgent need for effective methods to enhance the durability of artificial heart valves. Because oxidative stress (OS) is a key driving factor contributing to the failure of cardiovascular implants, this review focuses on how OS plays a critical role in heart valve degeneration, and its relationship with four major physiological mechanisms: extracellular matrix (ECM) degradation, immune response, thrombosis and lipid metabolism. By highlighting OS as a potential therapeutic target, we explore surface modification strategies that incorporate these fundamental mechanisms, refer to passive approaches including OS elimination, immunosuppression, blocking surface-degradation active groups, and anticoagulation, and active approaches such as regulating biological function recovery, and surface endothelial remodeling. These strategies aim to delay or reverse artificial valves degeneration via combining with the perspective of OS regulation, ultimately extending the prognosis period after heart valve replacement surgeries.

瓣膜性心脏病(VHD)是一种严重威胁公众健康的疾病,心脏瓣膜置换手术是治疗严重病例的标准方法。尽管人工心脏瓣膜技术不断进步,但由于体内退化,其寿命仍然有限。因此,迫切需要有效的方法来提高人工心脏瓣膜的耐用性。由于氧化应激(OS)是导致心血管植入物失效的一个关键驱动因素,本综述将重点探讨氧化应激如何在心脏瓣膜退化中发挥关键作用,以及它与细胞外基质(ECM)降解、免疫反应、血栓形成和脂质代谢这四大生理机制之间的关系。通过强调OS是潜在的治疗靶点,我们探讨了结合这些基本机制的表面修饰策略,包括消除OS、免疫抑制、阻断表面降解活性基团和抗凝等被动方法,以及调节生物功能恢复和表面内皮重塑等主动方法。这些策略旨在结合OS调节的观点,延缓或逆转人工瓣膜的退化,最终延长心脏瓣膜置换手术后的预后期。
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引用次数: 0
The state-of-the-art therapeutic paradigms against sepsis 最先进的败血症治疗范例
Q1 Engineering Pub Date : 2024-09-01 DOI: 10.1016/j.smaim.2024.08.005
Ishita Saha , Neelanjana Bag , Shubham Roy , Zia Ullah , Souravi Bardhan , Parimal Karmakar , Sukhen Das , Bing Guo

Sepsis frequently leads to life-threatening organ failure due to an in appropriate response by the body to bacterial, viral, and fungal infections. In recent years, there has been an increasing interest in using nanoparticles to develop biomarkers and drug delivery systems that have significantly improved the treatment of infectious diseases. Herein, we update the most recent development of nanoparticle-based therapeutics for sepsis treatment. This article begins with a brief overview of how sepsis is triggered and its associated diseases. It also explores the differences between traditional and modern treatment approaches. Afterward, the reasons for embracing nanotechnology-based therapies for sepsis are summarized, including their ability to reduce inflammation, provide antioxidant effects, regulate cell signaling pathways, manage reactive oxygen and nitrogen species (RONS) production, control autophagy and apoptosis, clear lipopolysaccharides (LPS) from the blood, inhibits the formation of cell-free DNA and cytokine storms. Furthermore, the special emphasis is on updating the use of nanotechnology-mediated drug delivery systems, such as nanoparticles, liposomes, and exosomes, in the treatment of sepsis caused by various microorganisms. Moreover, we also discuss polymer mediated therapy and some dynamic therapeutic aspects in septecemia disease. In addition, the article highlights the challenges and a limitation associated with using drug delivery for sepsis treatment and expresses the hope that this review will accelerate the development of more effective sepsis therapies and facilitate the transition from research to practical clinical application.

由于机体对细菌、病毒和真菌感染的反应不当,败血症经常导致危及生命的器官衰竭。近年来,人们对使用纳米粒子开发生物标记物和给药系统的兴趣与日俱增,这极大地改善了感染性疾病的治疗。在此,我们将介绍基于纳米粒子的败血症治疗方法的最新进展。本文首先简要概述了败血症的诱发原因及其相关疾病。文章还探讨了传统治疗方法与现代治疗方法之间的差异。随后,总结了采用基于纳米技术的败血症疗法的原因,包括它们能够减轻炎症、提供抗氧化效果、调节细胞信号通路、管理活性氧和氮物种(RONS)的产生、控制自噬和细胞凋亡、清除血液中的脂多糖(LPS)、抑制游离 DNA 的形成和细胞因子风暴。此外,我们还特别强调了纳米技术介导的给药系统(如纳米颗粒、脂质体和外泌体)在治疗由各种微生物引起的败血症方面的最新应用。此外,我们还讨论了聚合物介导疗法以及败血症的一些动态治疗方面。此外,文章还强调了利用药物递送治疗败血症所面临的挑战和局限性,并希望这篇综述能加快开发更有效的败血症疗法,促进从研究到实际临床应用的过渡。
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引用次数: 0
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