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Beamforming Design for Hybrid IRS-aided AF Relay Wireless Networks 混合 IRS 辅助 AF 中继无线网络的波束成形设计
1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-23 DOI: 10.48550/arXiv.2311.13893
Xuehui Wang, Yifan Zhao, Feng Shu, Yan Wang
In this paper, a hybrid IRS-aided amplify-and-forward (AF) relay wireless network is put forward, where the hybrid IRS is made up of passive and active elements. For maximum signal-to-noise ratio (SNR), a low-complexity method based on successive convex approximation and fractional programming (LC-SCA-FP) is proposed to jointly optimize the beamforming matrix at AF relay and the reflecting coefficient matrices at IRS. Simulation results verify that the rate achieved by the proposed LC-SCA-FP method surpass those of the benchmark schemes, namely the passive IRS-aided AF relay and only AF relay network.
本文提出了一种混合 IRS 辅助放大前向(AF)中继无线网络,其中混合 IRS 由无源和有源元件组成。为了获得最大信噪比(SNR),本文提出了一种基于逐次凸逼近和分数编程(LC-SCA-FP)的低复杂度方法,用于联合优化 AF 中继的波束成形矩阵和 IRS 的反射系数矩阵。仿真结果验证了所提出的 LC-SCA-FP 方法实现的速率超过了基准方案,即无源 IRS 辅助 AF 中继和仅 AF 中继网络。
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引用次数: 0
Smart stimuli-responsive drug delivery systems in spotlight of COVID-19 2019冠状病毒病疫情下的智能刺激反应性药物输送系统
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100873
Zeinab Najjari, Farzaneh Sadri, Jaleh Varshosaz

The world has been dealing with a novel severe acute respiratory syndrome (SARS-CoV-2) since the end of 2019, which threatens the lives of many people worldwide. COVID-19 causes respiratory infection with different symptoms, from sneezing and coughing to pneumonia and sometimes gastric symptoms. Researchers worldwide are actively developing novel drug delivery systems (DDSs), such as stimuli-responsive DDSs. The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating "smart" DDS that can effectively control dosage, sustained release, individual variations, and targeted delivery. To conduct a comprehensive literature survey for this article, the terms “Stimuli-responsive”, “COVID-19″ and “Drug delivery” were searched on databases/search engines like “Google Scholar”, “NCBI”, “PubMed”, and “Science Direct”. Many different types of DDSs have been proposed, including those responsive to various exogenous (light, heat, ultrasound and magnetic field) or endogenous (microenvironmental changes in pH, ROS and enzymes) stimuli. Despite significant progress in DDS research, several challenging issues must be addressed to fill the gaps in the literature. Therefore, this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.

自2019年底以来,世界一直在应对一种新型严重急性呼吸系统综合征(SARS-CoV-2),威胁着全世界许多人的生命。COVID-19引起的呼吸道感染有不同的症状,从打喷嚏和咳嗽到肺炎,有时还会出现胃部症状。世界各地的研究人员正在积极开发新的药物传递系统(dds),如刺激反应性dds。这些载体对外部/内部甚至多种刺激的反应能力对于创造能够有效控制剂量、缓释、个体变化和靶向给药的“智能”DDS至关重要。为了对本文进行全面的文献调查,我们在“Google Scholar”、“NCBI”、“PubMed”和“Science Direct”等数据库/搜索引擎上检索了“刺激响应”、“COVID-19”和“药物递送”等术语。人们提出了许多不同类型的dds,包括响应各种外源(光、热、超声和磁场)或内源(pH、ROS和酶的微环境变化)刺激的dds。尽管DDS研究取得了重大进展,但必须解决几个具有挑战性的问题以填补文献中的空白。因此,本研究综述了内源性/外源性刺激反应性dds的药物释放机制和应用,同时探讨了它们在COVID-19中的潜力。
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引用次数: 0
CRISPR/Cas9 systems: Delivery technologies and biomedical applications CRISPR/Cas9系统:传递技术和生物医学应用
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100854
Yimin Du , Yanfei Liu , Jiaxin Hu , Xingxing Peng , Zhenbao Liu

The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has brought about a significant revolution in the realm of managing human diseases, establishing animal models, and so on. To fully harness the potential of this potent gene-editing tool, ensuring efficient and secure delivery to the target site is paramount. Consequently, developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research. In this review, we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system. We also provide an in-depth analysis of physical, viral vector, and non-viral vector delivery strategies, including plasmid-, mRNA- and protein-based approach. In addition, we illustrate the biomedical applications of the CRISPR/Cas9 system. This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system, while also delineating future directions and prospects that could inspire innovative delivery strategies. This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.

聚类规则间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9 (Cas9)基因组编辑系统的出现,在人类疾病管理、建立动物模型等领域带来了重大变革。为了充分利用这种强大的基因编辑工具的潜力,确保高效和安全的递送到目标位点是至关重要的。因此,为CRISPR/Cas9系统开发有效的递送方法已成为一个关键的研究领域。在这篇综述中,我们全面概述了递送策略,并讨论了它们在CRISPR/Cas9系统中的生物医学应用。我们还提供了物理,病毒载体和非病毒载体递送策略的深入分析,包括质粒,mRNA和蛋白质为基础的方法。此外,我们说明了CRISPR/Cas9系统的生物医学应用。这篇综述强调了影响递送过程的关键因素和CRISPR/Cas9系统当前面临的挑战,同时也描绘了未来的方向和前景,可以激发创新的递送策略。本综述旨在为推进基于CRISPR/ cas9的递送策略提供新的见解和思路,促进生物医学研究和治疗应用的突破。
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引用次数: 0
Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider 探索纳米乳剂联合冰片作为导引剂经鼻给药增强药物在脑亚区分布的潜力
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100778
Xin Shen, Zhixiang Cui, Yidan Wei, Yingnan Huo, Duo Yu, Xin Zhang, Shirui Mao

The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. In vivo behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VINNE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.

阿尔茨海默病(AD)患者数量逐年增加,病灶主要集中在皮层和海马。尽管进行了许多努力,但由于血脑屏障(BBB)和AD病灶部位药物分布有限,有效治疗AD仍面临巨大挑战。因此,本研究以长春西汀(vinpocetine, VIN)为模型药物,探讨以纳米乳(NE)为载体,联合脑导剂冰片(BOR)经鼻给药解决上述瓶颈的可行性。首先,对NE进行了制备和表征。研究了NE经鼻给药后的体内行为。评价BOR剂量、给药途径对药物脑靶向行为的影响,探讨添加BOR对药物脑亚区分布的影响。经鼻给药后,所有的NE具有相当的大小和相似的保留行为。与静脉注射相比,鼻内途径脑靶向效果明显改善,VINNE组药物靶向指数(DTI)为154.1%,鼻脑直接转运率(DTP)为35.1%。特别是在NE中添加BOR后,脑分布明显增强,其程度取决于BOR的剂量。在BOR剂量为1 mg/kg时,VIN-1-BOR- ne组脑内VIN浓度最高,DTI达到596.1%,DTP增加至83.1%。经鼻给药时,BOR能更好地发挥鼻至脑输送作用。值得注意的是,BOR可以显著增强阿尔茨海默病病灶区海马和皮层的药物分布。综上所述,结合鼻内给药和BOR固有的脑引导作用,不仅可以显著增强药物在大脑内的分布,还可以显著增强药物在皮层和海马区的分布,为提高AD的治疗效果提供了条件。
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引用次数: 1
Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence 基于工程外泌体的肿瘤转移和复发治疗策略
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100870
Min Deng , Shuang Wu , Peizheng Huang , Yun Liu , Chong Li , Ji Zheng

Metastasis-associated processes are the predominant instigator of fatalities linked to cancer, wherein the pivotal role of circulating tumor cells lies in the resurgence of malignant growth. In recent epochs, exosomes, constituents of the extracellular vesicle cohort, have garnered attention within the field of tumor theranostics owing to their inherent attributes encompassing biocompatibility, modifiability, payload capacity, stability, and therapeutic suitability. Nonetheless, the rudimentary functionalities and limited efficacy of unmodified exosomes curtail their prospective utility. In an effort to surmount these shortcomings, intricate methodologies amalgamating nanotechnology with genetic manipulation, chemotherapy, immunotherapy, and optical intervention present themselves as enhanced avenues to surveil and intercede in tumor metastasis and relapse. This review delves into the manifold techniques currently employed to engineer exosomes, with a specific focus on elucidating the interplay between exosomes and the metastatic cascade, alongside the implementation of tailored exosomes in abating tumor metastasis and recurrence. This review not only advances comprehension of the evolving landscape within this domain but also steers the trajectory of forthcoming investigations.

转移相关过程是与癌症相关的死亡的主要诱因,其中循环肿瘤细胞的关键作用在于恶性生长的复苏。近年来,外泌体作为细胞外囊泡群的组成部分,由于其固有的生物相容性、可修饰性、有效载荷能力、稳定性和治疗适应性等特性,在肿瘤治疗领域引起了人们的关注。然而,未经修饰的外泌体的基本功能和有限的功效限制了它们的潜在效用。为了克服这些缺点,将纳米技术与基因操作、化疗、免疫治疗和光学干预相结合的复杂方法成为监测和干预肿瘤转移和复发的增强途径。本综述深入研究了目前用于外泌体工程的多种技术,重点阐述了外泌体与转移级联之间的相互作用,以及定制外泌体在减少肿瘤转移和复发方面的实施。这篇综述不仅促进了对这一领域内不断发展的景观的理解,而且指导了即将进行的调查的轨迹。
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引用次数: 0
Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma 雷公桃红素脂质体直接靶向VDAC2诱导肝癌细胞铁下垂和凋亡的机制工程
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100874
Piao Luo , Qian Zhang , Shuo Shen , Yehai An , Lixia Yuan , Yin-Kwan Wong , Sizhe Huang , Shaohui Huang , Jingnan Huang , Guangqing Cheng , Jiahang Tian , Yu Chen , Xiaoyong Zhang , Weiguang Li , Songqi He , Jigang Wang , Qingfeng Du

Hepatocellular carcinoma (HCC) is one of most common and deadliest malignancies. Celastrol (Cel), a natural product derived from the Tripterygium wilfordii plant, has been extensively researched for its potential effectiveness in fighting cancer. However, its clinical application has been hindered by the unclear mechanism of action. Here, we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and anti-tumor capacity by developing a Cel-based liposomes in HCC. We demonstrated that Cel selectively targets the voltage-dependent anion channel 2 (VDAC2). Cel directly binds to the cysteine residues of VDAC2, and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore (mPTP) function. We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells. Moreover, coencapsulation of Cel into alkyl glucoside-modified liposomes (AGCL) improved its antitumor efficacy and minimized its side effects. AGCL has been shown to effectively suppress the proliferation of tumor cells. In a xenograft nude mice experiment, AGCL significantly inhibited tumor growth and promoted apoptosis. Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death, while the Cel liposomes enhance its targetability and reduces side effects. Overall, Cel shows promise as a therapeutic agent for HCC.

肝细胞癌(HCC)是最常见和最致命的恶性肿瘤之一。雷公藤红素(Celastrol)是一种从雷公藤植物中提取的天然产物,因其抗癌的潜在功效而被广泛研究。但其作用机制尚不明确,阻碍了其临床应用。在这里,我们使用化学蛋白质组学来确定细胞的直接靶点,并通过在HCC中开发基于细胞的脂质体来增强其靶向性和抗肿瘤能力。我们证明了细胞选择性地靶向电压依赖性阴离子通道2 (VDAC2)。细胞直接与VDAC2的半胱氨酸残基结合,并通过VDAC2介导的线粒体通透性过渡孔(mPTP)功能失调诱导细胞色素C释放。我们进一步发现,细胞诱导ros介导的肝癌细胞铁下垂和凋亡。此外,将细胞共包被烷基葡萄糖苷修饰脂质体(AGCL)提高了其抗肿瘤效果,并将其副作用降至最低。AGCL已被证明能有效抑制肿瘤细胞的增殖。在异种移植裸鼠实验中,AGCL显著抑制肿瘤生长,促进细胞凋亡。我们的研究结果表明,细胞直接靶向VDAC2诱导线粒体依赖性细胞死亡,而细胞脂质体增强了其靶向性并减少了副作用。总之,细胞显示出作为HCC治疗药物的前景。
{"title":"Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma","authors":"Piao Luo ,&nbsp;Qian Zhang ,&nbsp;Shuo Shen ,&nbsp;Yehai An ,&nbsp;Lixia Yuan ,&nbsp;Yin-Kwan Wong ,&nbsp;Sizhe Huang ,&nbsp;Shaohui Huang ,&nbsp;Jingnan Huang ,&nbsp;Guangqing Cheng ,&nbsp;Jiahang Tian ,&nbsp;Yu Chen ,&nbsp;Xiaoyong Zhang ,&nbsp;Weiguang Li ,&nbsp;Songqi He ,&nbsp;Jigang Wang ,&nbsp;Qingfeng Du","doi":"10.1016/j.ajps.2023.100874","DOIUrl":"10.1016/j.ajps.2023.100874","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is one of most common and deadliest malignancies. Celastrol (Cel), a natural product derived from the <em>Tripterygium wilfordii</em> plant, has been extensively researched for its potential effectiveness in fighting cancer. However, its clinical application has been hindered by the unclear mechanism of action. Here, we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and anti-tumor capacity by developing a Cel-based liposomes in HCC. We demonstrated that Cel selectively targets the voltage-dependent anion channel 2 (VDAC2). Cel directly binds to the cysteine residues of VDAC2, and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore (mPTP) function. We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells. Moreover, coencapsulation of Cel into alkyl glucoside-modified liposomes (AGCL) improved its antitumor efficacy and minimized its side effects. AGCL has been shown to effectively suppress the proliferation of tumor cells. In a xenograft nude mice experiment, AGCL significantly inhibited tumor growth and promoted apoptosis. Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death, while the Cel liposomes enhance its targetability and reduces side effects. Overall, Cel shows promise as a therapeutic agent for HCC.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623001009/pdfft?md5=e8710b9808d908f1af5d0d3686da10d9&pid=1-s2.0-S1818087623001009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544268","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
A nanocomposite competent to overcome cascade drug resistance in ovarian cancer via mitochondria dysfunction and NO gas synergistic therapy 一种纳米复合材料能够通过线粒体功能障碍和NO气体协同治疗克服卵巢癌的级联耐药
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100872
Min Zhong , Peiqin Liang , Zhenzhen Feng , Xin Yang , Guang Li , Rui Sun , Lijuan He , Jinxiu Tan , Yangpengcheng Xiao , Zhiqiang Yu , Muhua Yi , Xuefeng Wang

Ovarian cancer (OC) is one of the most common and recurring malignancies in gynecology. Patients with relapsed OC always develop "cascade drug resistance" (CDR) under repeated chemotherapy, leading to subsequent failure of chemotherapy. To overcome this challenge, amphiphiles (P1) carrying a nitric oxide (NO) donor (Isosorbide 5-mononitrate, ISMN) and high-density disulfide are synthesized for encapsulating mitochondria-targeted tetravalent platinum prodrug (TPt) to construct a nanocomposite (INP@TPt). Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum, depleting glutathione, and preventing apoptosis escape through generating highly toxic peroxynitrite anion (ONOO). To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor, an OC patient-derived tumor xenograft (PDXOC) model in BALB/c nude mice was established. INP@TPt showed the best therapeutic effects in the PDXOC model. The corresponding tumor tissues contained high ONOO levels, which were attributed to the simultaneous release of O2•− and NO in tumor tissues. Taken together, INP@TPt-based systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR, providing practical applications for ovarian therapy.

卵巢癌(OC)是妇科最常见和复发的恶性肿瘤之一。复发性卵巢癌患者在反复化疗下往往会出现“级联耐药”(CDR),导致后续化疗失败。为了克服这一挑战,两亲体(P1)携带一氧化氮(NO)供体(ISMN)和高密度二硫化合物,用于包封线粒体靶向四价铂前药(TPt),构建纳米复合材料(INP@TPt)。机制研究表明,INP@TPt通过增加铂的细胞摄取和线粒体积累,消耗谷胱甘肽,并通过产生高毒性过氧亚硝酸盐阴离子(ONOO−)阻止细胞凋亡逃逸,从而显著抑制耐药细胞。为了更好地复制耐药原发肿瘤的微环境和组织学特征,在BALB/c裸鼠中建立OC患者源性肿瘤异种移植(PDXOC)模型。INP@TPt对PDXOC模型的治疗效果最好。相应的肿瘤组织中ONOO−含量较高,这是由于肿瘤组织中O2•−和NO同时释放所致。综上所述,INP@TPt-based系统策略在克服铂CDR方面显示出相当大的潜力和令人满意的生物相容性,为卵巢治疗提供了实际应用。
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引用次数: 0
Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche 纳米治疗药物进入骨髓生态位关键细胞群的初步递送效率预测
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100868
Huijuan Chen , Anzhi Hu , Mengdi Xiao , Shiyi Hong , Jing Liang , Quanlong Zhang , Yang Xiong , Mancang Gu , Chaofeng Mu

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs in vivo was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (<1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro. This study provided the methodology for niche-directed nanotherapeutics development.

几个关键的基质细胞群调节造血和骨髓龛中的恶性疾病。对这些细胞类型的精确调控可以重塑生态位并开发新的治疗方法。多种纳米载体已经被开发出来,可以选择性地将药物运送到骨髓中。然而,这些纳米治疗药物在关键生态位细胞中的递送效率仍然未知,并且没有可用的方法来预测这些细胞类型的递送效率。在这里,我们构建了一个由三个关键细胞群组成的三维骨髓生态位:内皮细胞(ECs)、间充质基质细胞(MSCs)和成骨细胞(OBs)。采用模拟壁龛法检测三种典型药物纳米载体在体外对ECs/MSCs/OBs的细胞摄取。三种基质细胞占纳米载体的比例均不到5%,且大部分位于细胞外基质中。在体内分析正弦内皮细胞、小动脉内皮细胞、间充质干细胞和OBs的传递效率。相关分析表明,三种纳米载体在体外对关键细胞类型的细胞摄取与其在体内的递送效率呈线性正相关。无论何种纳米载体,MSCs的递送效率均显著高于ECs和OBs。进入正弦波内皮细胞的总效率远低于进入小动脉内皮细胞的总效率。所有纳米载体都难以进入OBs (<1%)。我们的研究结果表明,不同组成和配体附着的纳米载体在体内的细胞趋向性可以通过检测其在体外骨髓壁龛中的细胞摄取来预测。本研究为小生境定向纳米疗法的开发提供了方法学依据。
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引用次数: 0
Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery 释放愈合潜力:探索用于烧伤伤口恢复的下一代再生蛋白质纳米支架
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100856
Liangwei Si , Xiong Guo , Hriday Bera , Yang Chen , Fangfang Xiu , Peixin Liu , Chunwei Zhao , Yasir Faraz Abbasi , Xing Tang , Vito Foderà , Dongmei Cun , Mingshi Yang

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen sponge on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

烧伤是一个严重的公共卫生问题,科学家们一直致力于开发有前途的仿生敷料,以有效地管理烧伤创面。在本研究中,我们建立了基于α-乳清蛋白(ALA)的静电纺纳米纤维支架(ENs)与其他再生蛋白支架相比,在烧伤创面愈合中的更大功效及其相关机制。将牛血清白蛋白(BSA)、ⅰ型胶原蛋白(COL)、溶菌酶(LZM)和ALA分别与聚ε-己内酯(PCL)共混制得4种不同的复合ENs (LZM/PCL、BSA/PCL、COL/PCL和ALA/PCL ENs)。亲水性复合支架表现出增强的润湿性和可变的力学性能。ALA/PCL ENs比其他复合材料ENs具有更高的成纤维细胞增殖和粘附水平,与PCL ENs和其他复合材料支架相比,ALA/PCL ENs还能促进再生皮肤组织的成熟,并在三度烧伤模型上表现出与胶原海绵Ⓡ相当的伤口愈合效果。与其他ENs相比,ALA/PCL ENs的伤口愈合活性增强可能归因于它们促进伤口部位血清素产生的能力。总的来说,这项研究表明,与其他再生蛋白相比,ALA是一种独特的蛋白质,当负载在纳米纤维支架中时,它具有更大的烧伤伤口愈合潜力。
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引用次数: 0
Leveraging immunoliposomes as nanocarriers against SARS-CoV-2 and its emerging variants 利用免疫脂质体作为纳米载体对抗SARS-CoV-2及其新变体
IF 10.2 1区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-01 DOI: 10.1016/j.ajps.2023.100855
Nur Dini Fatini Mohammad Faizal , Nurul Afina Ramli , Nur Najihah Izzati Mat Rani , Nur Adania Shaibie , Aarti , Pattaporn Poonsawas , Sunil K. Sharma , Mohd Cairul Iqbal Mohd Amin

The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives, gaining interest worldwide ever since it was first identified in December 2019. Till 2023, 752 million cumulative cases and 6.8 million deaths were documented globally. COVID-19 has been rapidly evolving, affecting virus transmissibility and properties and contributing to increased disease severity. The Omicron is the most circulating variant of concern. Although success in its treatment has indicated progress in tackling the virus, limitations in delivering the current antiviral agents in battling emerging variants remain remarkable. With the latest advancements in nanotechnology for controlling infectious diseases, liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies, incorporating monoclonal antibodies for the active and passive targeting of infected patients. This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARS-CoV-2 and its variants.

由SARS-CoV-2引起的全球COVID-19大流行影响了许多人的生活,自2019年12月首次发现以来,它引起了全世界的关注。到2023年,全球累计记录了7.52亿例病例和680万例死亡。COVID-19迅速演变,影响了病毒的传播性和性质,并导致疾病严重程度增加。欧米克隆是最流行的担忧变体。尽管这种治疗方法的成功表明,在对付这种病毒方面取得了进展,但目前的抗病毒药物在对抗新出现的变种方面仍然存在显著的局限性。随着纳米技术在控制传染病方面的最新进展,脂质体具有对抗SARS-CoV-2的潜力,因为它们能够采用不同的靶向策略,将单克隆抗体纳入主动和被动靶向感染患者。本综述将简要总结利用免疫脂质体改善当前治疗SARS-CoV-2及其变体的可能策略。
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Asian Journal of Pharmaceutical Sciences
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