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Anti-inflammatory, antibacterial, and antioxidative bioactive glass-based nanofibrous dressing enables scarless wound healing 抗炎,抗菌,抗氧化的生物活性玻璃基纳米纤维敷料使伤口愈合无疤痕
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.01.001
Zhengchao Yuan , Lixiang Zhang , Shichao Jiang , Muhammad Shafiq , Youjun Cai , Yujie Chen , Jiahui Song , Xiao Yu , Hiroyuki Ijima , Yuan Xu , Xiumei Mo

Excessive scar tissue formation along with bacterial infection, hemorrhage, and oxidative wound microenvironment pose adverse physiological and psychological effects on patients, which necessitate the advent of innovative anti-inflammatory, anti-bacterial, and anti-oxidative multifunctional wound dressings. The overarching objective of this study was to exploit bioactive glass (BG) and a natural anti-bacterial component namely “oregano essential oil (OEO)” to impart multifunctionality to poly(L-lactide-co-glycolide)/Gelatin (PLGA/Gel)-based nanofibrous dressings for excisional wound management. We performed a series of structural, morphological, and release studies as well as delineated angiogenic, hemostatic, anti-bacterial, and anti-oxidative properties of these bioactive dressings in vitro, which altogether revealed the beneficial effects of BG and OEO in terms of rapid hemostasis, improved chemotactic response, diminished bacterial colonization, and anti-inflammatory response. Impressively, in multiple injury models, including a rat tail-amputation model, an ear artery injury model, and a liver trauma model in rabbit in vivo, we reported BG-mediated rapid hemostasis. Moreover, dressings containing BG showed improved hemocompatibility and suppressed coagulation as revealed by activated partial thromboplastin assay (APTT) in vitro. In addition, the transplantation of these nanofibrous dressings in a full-thickness excisional wound model in rats showed significant tissue regeneration as evidenced by the more number of blood vessels, glands, and hair follicles, re-epithelialization, diminished inflammatory response, and less fibrotic tissue formation. Taken together our approach of simultaneously harnessing economical BG and OEO to enable multifunctionality to nanofibrous dressings for tissue repair may hold great promise for wound healing as well as other bio-related disciplines.

过度的疤痕组织形成以及细菌感染、出血和氧化伤口微环境对患者造成了不利的生理和心理影响,这就需要创新的抗炎、抗菌和抗氧化多功能伤口敷料的出现。本研究的首要目标是利用生物活性玻璃(BG)和一种天然抗菌成分,即“牛至精油(OEO)”,赋予聚L-丙交酯-共-甘醇内酯/明胶(PLGA/Gel)基纳米纤维敷料多功能性,用于切除性伤口管理。我们进行了一系列结构、形态学和释放研究,并在体外描述了这些生物活性敷料的血管生成、止血、抗菌和抗氧化特性,这些特性共同揭示了BG和OEO在快速止血、改善趋化反应、减少细菌定殖和抗炎反应方面的有益作用。令人印象深刻的是,在多种损伤模型中,包括大鼠尾部截肢模型、耳动脉损伤模型和兔体内肝损伤模型,我们报道了BG介导的快速止血。此外,含有BG的敷料显示出改善的血液相容性和抑制的凝血,如体外活化部分凝血活酶测定(APTT)所示。此外,在大鼠全层切除伤口模型中移植这些纳米纤维敷料显示出显著的组织再生,表现为更多的血管、腺体和毛囊,上皮化,炎症反应减少,纤维化组织形成减少。总之,我们同时利用经济的BG和OEO来实现用于组织修复的纳米纤维敷料的多功能性的方法可能对伤口愈合以及其他生物相关学科有很大的前景。
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引用次数: 6
In situ electrospun aloe-nanofiber membrane for chronic wound healing 原位静电纺芦荟纳米纤维膜用于慢性伤口愈合
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.03.003
Chang Liu , Yun Wang , Pei Wang , Yan Gong , Bingcheng Yi , Jing Ruan , Xiansong Wang

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

缓解过度炎症,同时加速慢性伤口愈合以预防伤口感染仍然具有挑战性,尤其是在由SARS-CoV-2引起的2019冠状病毒病(新冠肺炎)大流行期间,患者在获得适当的医疗保健方面遇到困难。我们通过开发手持式电纺芦荟纳米纤维膜(ANFMs)来解决这个问题,该膜具有方便、环保的特性和伤口闭合的治疗能力。我们的研究结果表明,用高分子量聚乙烯醇(PVA)在静电纺丝过程中制备的ANFM具有均匀的纤维结构和多孔结构。鉴于芦荟凝胶在加速伤口愈合方面的价值,ANFMs的液体提取物显著下调促炎基因白细胞介素-6(IL-6)和诱导型一氧化氮合酶(iNOS)的表达,并显著抑制脂多糖诱导的RAW264.7巨噬细胞中活性氧(ROS)的产生。这些结果表明ANFMs具有良好的抗氧化和抗炎作用。在原位植入小鼠糖尿病伤口模型12天后,ANFMs通过促进血管生成和增强细胞活力显著加速了慢性伤口愈合。我们的ANFM由手持式静电纺丝原位愈合的慢性伤口产生,为患者在不同条件下治愈自己的伤口提供了一种方便且有前景的替代方案。
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引用次数: 1
Core-shell nanostructures for improving dental restorative materials: A scoping review of composition, methods, and outcome 改善牙齿修复材料的核壳纳米结构:组成,方法和结果的范围审查
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.08.002
Lamia Sami Mokeem , Isadora Martini Garcia , Yasmin Shahkarami , Lauren Blum , Abdulrahman A. Balhaddad , Fabrício Mezzomo Collares , Mary Ann Williams , Michael D. Weir , Mary Anne S. Melo

Dental resin adhesives and composites are the most prevailing dental restorative materials used to treat cavitated tooth decay. These materials are challenged inside the mouth by bacterial acid attack, lack of bioactivity, and the scarcity of alternatives maintaining the mechanical properties over the lifetime service of these materials. Core-shell nanostructures are composed of various materials surrounded by a protective shell. They are acquiring considerable attention as innovative multipurpose carriers that show great potential in restorative dentistry. Herein, we systematically reviewed the recent studies on core-shell nanostructures incorporated into dental resin-based materials, their intended properties, synthesis methods, and assessment tests employed. This study used scoping review method, following Arksey and O'Malley's five stages framework using PubMed and Scopus (Elsevier) databases. From 149 initially identified manuscripts, 20 studies were eligible for full-text screening, and 15 were included for data extraction. The majority of included studies have used resin composite as parental material. Silica oxide was the most prevailing shell incorporated into dental resins. Almost all core-shell nanostructures were added to improve the material's strength and impart antibacterial properties. Designing strategies and drug release behaviors were discussed. In the end, current challenges and prospects in this promising field were highlighted.

牙科树脂粘接剂和复合材料是最常用的牙科修复材料,用于治疗空腔性蛀牙。这些材料在口腔内受到细菌酸攻击的挑战,缺乏生物活性,并且缺乏替代品来维持这些材料的机械性能。核壳纳米结构是由被保护壳包围的各种材料组成的。它们作为创新性的多用途载体,在牙科修复中显示出巨大的潜力,正受到越来越多的关注。在此,我们系统地回顾了最近的研究,核壳纳米结构纳入牙科树脂基材料,他们的预期性能,合成方法和评估测试采用。本研究采用范围审查方法,遵循Arksey和O'Malley的五阶段框架,使用PubMed和Scopus (Elsevier)数据库。从最初确定的149篇论文中,20篇研究符合全文筛选条件,15篇纳入数据提取。大多数纳入的研究都使用树脂复合材料作为母材。氧化硅是最普遍的外壳纳入牙科树脂。几乎所有的核壳纳米结构都是为了提高材料的强度和抗菌性能而添加的。讨论了设计策略和药物释放行为。最后,对该领域当前面临的挑战和前景进行了展望。
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引用次数: 4
Promotion of osteoporotic bone healing by a tannic acid modified strontium-doped biomimetic bone lamella with ROS scavenging capacity and pro-osteogenic effect 具有ROS清除能力和促成骨作用的单宁酸修饰的锶掺杂仿生骨片促进骨质疏松性骨愈合
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.05.001
Zhenzhen Wu , Le Fan , Cuiting Chen , Yuanyuan Ma , Xiangnan Wu , Ying Li , Zhichao Hao , Tao Yang

The impaired osteogenic ability and excessive accumulation of reactive oxygen species (ROS) under osteoporosis severely weaken repair performance of biomimetic bone grafts. Currently, biomimetic bone grafts, capable of highly simulating bone hierarchy, could remarkably promote bone regeneration without systemic disease. Decorating biomimetic bone grafts with bioactivities without compromising hierarchical biomimicry stands as a feasible approach to treat the osteoporotic bone defect. Herein, through mineralizing decellularized collagen lamellae via strontium (Sr)- amorphous calcium phosphate and further modifying with tannic acid (TA), TA modified Sr-doped biomimetic bone lamellae was engineered. The physicochemical properties, ROS scavenging capacity and pro-osteogenic effect on osteoporotic bone marrow mesenchymal stem cells of construct were systemically evaluated. The results showed that TA and Sr can be successfully decorated without impairing the nano- and micro-architecture of biomimetic bone lamellae. The construct not only exhibited a potent and long-standing performance to eliminate ROS, but also effectively fostered the proliferation and osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells under oxidative stress environment. After implantation in the critical-sized bone defect of osteoporotic rat, it potently facilitated bone regeneration via synergistically activating PI3K/AKT signaling pathway. Hence, this construct is projected to be candidate for further engineering biomimetic bone grafts with more complicated hierarchy for accelerated healing of the osteoporotic bone defect.

骨质疏松症下的成骨能力受损和活性氧(ROS)的过度积累严重削弱了仿生骨移植的修复性能。目前,仿生骨移植物能够高度模拟骨层次,可以显著促进骨再生,而不会引起全身性疾病。在不影响层次仿生学的情况下,修饰具有生物活性的仿生骨移植物是治疗骨质疏松性骨缺损的可行方法。本文通过锶-无定形磷酸钙矿化脱细胞胶原片层,并用单宁酸(TA)进一步修饰,构建了TA修饰的掺锶仿生骨片层。系统评价其对骨质疏松性骨髓间充质干细胞的理化性质、清除活性氧能力及促骨作用。结果表明,TA和Sr可以在不影响仿生骨片纳米结构和微结构的情况下成功修饰仿生骨片。该构建体不仅能长期有效地清除ROS,还能有效地促进氧化应激环境下骨质疏松性骨髓间充质干细胞的增殖和成骨分化。在骨质疏松大鼠临界尺寸骨缺损中植入后,通过协同激活PI3K/AKT信号通路,有效促进骨再生。因此,该结构有望成为未来具有更复杂层次结构的工程仿生骨移植物的候选材料,以加速骨质疏松性骨缺损的愈合。
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引用次数: 1
Function and treatment strategies of β-hydroxybutyrate in aging β-羟基丁酸酯在衰老中的作用及治疗策略
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.09.003
Yang Xiang , Qi-Quan Wang , Xin-Qiang Lan , Hui-Jie Zhang , Dai-Xu Wei

Metabolic intermediates serve as precursors for bioactive molecule synthesis, the energy source for life activities, and signals for environmental adaptation. Ketone bodies are important metabolic intermediates produced in the liver by the degradation of fatty acids, acting as an alternative energy source for extrahepatic tissues when glucose is short in supply (especially during starvation). β-hydroxybutyric acid, with its conjugate base β-hydroxybutyrate, constitutes approximately 70% of ketone bodies. A growing number of studies have demonstrated the beneficial effects of β-hydroxybutyrate, especially in delaying aging, intervening in aging-related disease, and promoting longevity. This review systematically reviews the role of β-hydroxybutyrate in aging hallmarks, shedding light on the possible molecular mechanism by which β-hydroxybutyrate supports healthy aging. Higher circulating β-hydroxybutyrate can be achieved by lifestyle modification (ketogenic diet or caloric restriction) or exogenous β-hydroxybutyrate (or β-hydroxybutyrate precursors, derivates and agonists) supplementation. We will also discuss the pros and cons of different ways to upregulate β-hydroxybutyrate, emphasizing the promising future clinical use of poly-β-hydroxybutyrate, the polymers of β-hydroxybutyrate, which can be easily produced via a microbial platform and synthetic biology.

代谢中间体是生物活性分子合成的前体,是生命活动的能量来源,是适应环境的信号。酮体是肝脏通过脂肪酸降解产生的重要代谢中间体,在葡萄糖供应不足时(特别是饥饿时)作为肝外组织的替代能量来源。β-羟基丁酸及其共轭碱β-羟基丁酸盐约占酮体的70%。越来越多的研究证明了β-羟基丁酸酯的有益作用,特别是在延缓衰老、干预衰老相关疾病和促进长寿方面。本文系统综述了β-羟基丁酸盐在衰老标志中的作用,揭示了β-羟基丁酸盐支持健康衰老的可能分子机制。可以通过改变生活方式(生酮饮食或热量限制)或补充外源性β-羟基丁酸盐(或β-羟基丁酸前体、衍生物和激动剂)来提高β-羟基丁酸盐的循环水平。我们还将讨论上调β-羟基丁酸盐的不同方法的利弊,强调β-羟基丁酸盐的聚合物聚β-羟基丁酸盐的临床应用前景广阔,它可以很容易地通过微生物平台和合成生物学来生产。
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引用次数: 3
Application of nanomedicine and mesenchymal stem cells in burn injuries for the elderly patients 纳米药物与间充质干细胞在老年烧伤患者中的应用
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.08.001
Wei Xiong , Rui Zhang , Heng Zhou , Ye Liu , Ming Liang , Keshen Li , Xingxiang Duan , David Pengcheng Chen , Yu Luo , Jia Xu , Yilong Ai , Yan He , Qingsong Ye

Burns not only damage the skin barrier, but also cause a series of inflammatory reactions and oxidative stress states. Among them, elderly patients are prone to suffer severe burns due to degenerative changes of their skin caused by aging factors, such as atrophy and thinning, etc. After burns, the body will continuously release inflammatory factors, resulting in systemic inflammatory response syndrome (SIRS) and oxidative stress, which are related to the poor treatment effect and the poor prognosis of elderly burn patients. It seems to be difficult for conventional treatments to control the disease development of elderly burn patients effectively. Considering the rapidly increasing elderly population, it is priority to understand the pathological process and the mechanisms to formulate more appropriate treatment strategies for elderly burn patients. In recent years, owing to considerable advances in nanotechnology, a variety of nanomaterials have been developed for wound healing and inflammation regulation. Its good biocompatibility, cell proliferation stimulation and antibacterial properties make the clinical treatment strategy more optimized. Concurrently, mesenchymal stem cells (MSCs) have also been used in the burns field and have been proven effective in not only controlling the level of inflammation and regulating the systemic immune balance, but also promoting wound healing and vascularization. Here, this review covers burns classification, the pathological process of elderly burn patients, and the research progress of nanotechnology and MSCs in burns. Eventually, we summarize the advantages and challenges of emerging strategies such as nanotechnology and MSCs in the treatment of elderly burn patients, expecting to promote the clinical transformation.

烧伤不仅会破坏皮肤屏障,还会引起一系列炎症反应和氧化应激状态。其中,老年患者由于衰老因素导致皮肤萎缩、变薄等退行性变化,容易发生严重烧伤。烧伤后,机体会不断释放炎症因子,导致全身炎症反应综合征(systemic inflammatory response syndrome, SIRS)和氧化应激,这与老年烧伤患者治疗效果差、预后差有关。传统的治疗方法似乎难以有效控制老年烧伤患者的病情发展。考虑到老年人口的快速增长,了解老年烧伤患者的病理过程和机制,制定更合适的治疗策略是当务之急。近年来,由于纳米技术的巨大进步,各种纳米材料被开发用于伤口愈合和炎症调节。其良好的生物相容性、刺激细胞增殖和抗菌性能使其临床治疗策略更加优化。同时,间充质干细胞(mesenchymal stem cells, MSCs)也被应用于烧伤领域,不仅在控制炎症水平和调节全身免疫平衡方面有效,而且还能促进伤口愈合和血管形成。本文就烧伤的分类、老年烧伤患者的病理过程以及纳米技术和间充质干细胞在烧伤中的研究进展进行综述。最后,我们总结了纳米技术和间充质干细胞等新兴策略在老年烧伤患者治疗中的优势和挑战,以期促进临床转型。
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引用次数: 3
Retraction notice to “Anti-microbial/oxidative/inflammatory nanogels accelerate chronic wound healing” [Smart Mater. Med. 3 (2022) 148–158] “抗菌/氧化/炎症纳米凝胶加速慢性伤口愈合”的撤回通知[Smart Mater.Med.3(2022)148–158]
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.04.003
Amit Nain , Yu-Ting Tseng , Akash Gupta , Yu-Feng Lin , Arumugam Sangili , Yu-Fen Huang , Chih-Ching Huang , Huan-Tsung Chang

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Due to the lack of agreement on affiliation format between authors and the owner of the journal, this article has been retracted at the request of all authors, the Editors-in-Chief and the owner of the journal.

本文已被撤回:请参见爱思唯尔文章撤回政策(https://www.elsevier.com/about/our-business/policies/article-withdrawal).Due)由于作者和期刊所有者之间缺乏关于归属格式的协议,应所有作者、主编和期刊所有者的要求,本文已被撤回。
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引用次数: 0
Metallic nanoscale-knife application in cancer theranostics 金属纳米刀在癌症治疗中的应用
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.11.006
Chunqiu Zhao , Fawad Ur Rehman , Sana Shaikh , Rida e Maria Qazi , Zahra Sajid , Afsar Ali Mian , Nongyue He

Nanoscale metal is considered the backbone of biomedical nanotechnology. Recently, there has been an exponential increase in nanoscale materials’ biomedical applications. These nanomaterials have mainly been employed in drug delivery systems, prosthetic implants, diagnostics, and therapeutics of various diseases, including cancer. Nanoscale materials have two major classes, namely organic and inorganic nanomaterials. Given the merit of excellent biocompatibility, facile synthesis, target recognition, prolonged circulation half-life, and deference to surface functionalization, the inorganic (metallic) nanoparticles hold promising applications in biomedicine. Their biomedical properties may vary based on their type, size, shape, structure, functionalization, and origin. This review will enlighten the recent advances in nanoscale materials applications as nanoscale-knife in cancer theranostics. Moreover, the external assisted technologies and metallic nanoparticle surface decoration will also be highlighted.

纳米金属被认为是生物医学纳米技术的支柱。近年来,纳米材料在生物医学领域的应用呈指数级增长。这些纳米材料主要应用于药物输送系统、假体植入物、各种疾病的诊断和治疗,包括癌症。纳米材料有两大类,即有机纳米材料和无机纳米材料。无机(金属)纳米颗粒具有良好的生物相容性、易于合成、目标识别、循环半衰期长、表面功能化等优点,在生物医学领域具有广阔的应用前景。它们的生物医学特性可能因其类型、大小、形状、结构、功能化和来源而异。本文综述了纳米材料作为纳米刀在肿瘤治疗中的应用进展。此外,还将重点介绍外部辅助技术和金属纳米颗粒表面修饰。
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引用次数: 1
A study involving PC-3 cancer cells and novel carbamate gemini surfactants: Is zeta potential the key to control adhesion to cells? 一项涉及PC-3癌症细胞和新型氨基甲酸酯双子表面活性剂的研究:ζ电位是控制细胞粘附的关键吗?
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.09.001
R.V. Pavlov, G.A. Gaynanova, D.M. Kuznetsov, Ya.A. Ivanov, S.K. Amerkhanova, A.P. Lyubina, A.D. Voloshina, L.Ya. Zakharova

Liposome surface potential effect on cellular uptake and cytotoxicity is evaluated using liposomes, modified with cationic lipid DOTAP, a series of cationic gemini surfactants with two carbamate fragments, and an amphiphilic peptide SSRGD. The surfactants used are novel representatives of the gemini family with improved self-assembling activity coupled with potential biodegradable properties and displayed increasing antibacterial activity and cytotoxicity with the shortening of hydrophobic alkyl tails. The longest alkyl tail surfactant, 14-6-14(Et), was the most biocompatible of the series, which was chosen for liposome modification. Prepared liposomes of various compositions are characterized from morphological and physicochemical standpoints in order to optimize their biocompatibility and stability. The carbamate gemini surfactants were also twice as effective at providing positive charge to liposomes and less toxic compared to DOTAP. On their own, carbamate surfactants were able to increase cellular uptake of liposomes by 190%. The mixed composition of 14-6-14(Et) surfactant and SSRGD amphiphilic peptide was the most readily absorbed formulation among different tested neutral, cationic and RGD-modified liposomes. The comparison between the cellular uptake promotion is conducted as to what is the most selective and efficient approach to enhance lipid nanoparticle uptake by cancerous cells.

脂质体表面电位对细胞摄取和细胞毒性的影响通过脂质体、阳离子脂质DOTAP、一系列带有两个氨基甲酸酯片段的阳离子gemini表面活性剂和两亲性肽SSRGD进行了评估。所使用的表面活性剂是gemini家族的新代表,具有改进的自组装活性以及潜在的生物降解性能,并且随着疏水烷基尾部的缩短而显示出增强的抗菌活性和细胞毒性。最长的烷基尾表面活性剂14-6-14(Et)是该系列中生物相容性最好的,被选择用于脂质体修饰。为了优化其生物相容性和稳定性,从形态和理化角度对制备的各种成分的脂质体进行了表征。氨基甲酸酯双子星表面活性剂为脂质体提供正电荷的效率是DOTAP的两倍,毒性更小。就其本身而言,氨基甲酸酯表面活性剂能够将脂质体的细胞摄取增加190%。其中,14-6-14(Et)表面活性剂与SSRGD两亲肽的混合配方是中性、阳离子和rgd修饰脂质体中最易吸收的配方。比较了促进细胞摄取的方法,以确定哪种方法最具选择性和最有效地增强了癌细胞对脂质纳米颗粒的摄取。
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引用次数: 4
Phospholipid-based nanodrill technology for enhanced intracellular delivery of nano-sized cargos 基于磷脂的纳米钻技术用于增强纳米级货物的细胞内递送
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.03.001
Doyeon Kim , Seung Soo Nam , Hyunbum Jeon , Youngheun Cho , Eunji Sim , Hyuncheol Kim

Nanosized drug delivery systems typically enter the cell via endocytosis. However, a significant amount of the endocytosed cargo cannot effectively escape from the endosome, resulting in drug degradation. Therefore, there are several ongoing efforts to develop transmembrane delivery systems that could circumvent endocytosis. In this study, phospholipid nanotube nanodrills (LDs) were formed onto the surface of a human serum albumin nanoparticle via self-assembling phospholipids. The nanodrill technology enhanced the intracellular uptake efficiency of nanoparticles via energy-independent direct cell membrane permeation. The length of the nanodrills according to the DSPE-PEG to DSPC ratio was investigated both experimentally and theoretically. Our findings demonstrated that longer nanodrills were formed on the surface of the nanoparticles as the ratio of DSPC (i.e., a strongly hydrophobic lipid) in the two phospholipids increases. Moreover, the intracellular uptake efficiency increased as the length of phospholipid nanodrills increased. In addition to enhancing intracellular delivery, the phospholipid nanodrills could penetrate the extracellular matrix and enable the introduction of nanoparticles, thus highlighting the promising tissue penetration capacity of phospholipid nanodrill technology. The improved cell permeability of LD technology was demonstrated by effectively inhibiting specific genes via siRNA-based therapeutic delivery. Moreover, this approach enhanced the efficacy of chemotherapeutics against chemo-resistant cancer cells. Therefore, LD technology could be used to deliver genetic materials and chemical-based therapeutics both in vitro and in vivo.

纳米级药物输送系统通常通过内吞作用进入细胞。然而,大量的内吞货物不能有效地从内核体中逃脱,导致药物降解。因此,有几个正在进行的努力,以开发跨膜传递系统,可以绕过内吞作用。本研究通过磷脂的自组装,在人血清白蛋白纳米颗粒表面形成磷脂纳米管纳米钻(ld)。纳米钻技术通过不依赖能量的直接细胞膜渗透提高了纳米颗粒在细胞内的摄取效率。实验和理论研究了DSPE-PEG与DSPC比对纳米钻长度的影响。我们的研究结果表明,随着两种磷脂中dsc(即一种强疏水脂质)的比例增加,纳米颗粒表面形成了更长的纳米钻。此外,细胞内摄取效率随磷脂纳米钻长度的增加而增加。除了增强细胞内递送外,磷脂纳米钻还可以穿透细胞外基质,从而使纳米颗粒的引入成为可能,从而突出了磷脂纳米钻技术有前途的组织渗透能力。通过基于sirna的治疗递送,LD技术可以有效抑制特定基因,从而提高细胞通透性。此外,这种方法提高了化疗药物对化疗耐药癌细胞的疗效。因此,LD技术可用于体外和体内传递遗传物质和化学疗法。
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Smart Materials in Medicine
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