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Targeting bacterial metabolites in tumor for cancer therapy: An alternative approach for targeting tumor-associated bacteria 针对肿瘤中的细菌代谢物进行癌症治疗:针对肿瘤相关细菌的另一种方法
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-02 DOI: 10.1016/j.addr.2024.115345
Guofeng Ji , Jingjing Zhao , Xinghui Si , Wantong Song

Emerging evidence reveal that tumor-associated bacteria (TAB) can facilitate the initiation and progression of multiple types of cancer. Recent work has emphasized the significant role of intestinal microbiota, particularly bacteria, plays in affecting responses to chemo- and immuno-therapies. Hence, it seems feasible to improve cancer treatment outcomes by targeting intestinal bacteria. While considering variable richness of the intestinal microbiota and diverse components among individuals, direct manipulating the gut microbiota is complicated in clinic. Tumor initiation and progression requires the gut microbiota-derived metabolites to contact and reprogram neoplastic cells. Hence, directly targeting tumor-associated bacteria metabolites may have the potential to provide alternative and innovative strategies to bypass the gut microbiota for cancer therapy. As such, there are great opportunities to explore holistic approaches that incorporates TAB-derived metabolites and related metabolic signals modulation for cancer therapy. In this review, we will focus on key opportunistic areas by targeting TAB-derived metabolites and related metabolic signals, but not bacteria itself, for cancer treatment, and elucidate future challenges that need to be addressed in this emerging field.

新的证据显示,肿瘤相关细菌(TAB)可促进多种类型癌症的发生和发展。最近的研究强调,肠道微生物群(尤其是细菌)在影响化疗和免疫疗法反应方面发挥着重要作用。因此,针对肠道细菌改善癌症治疗效果似乎是可行的。考虑到不同个体肠道微生物群的丰富程度和组成成分各不相同,直接操纵肠道微生物群在临床上是很复杂的。肿瘤的发生和发展需要肠道微生物群衍生的代谢物与肿瘤细胞接触并对其进行重编程。因此,直接以肿瘤相关细菌代谢物为靶点,有可能提供绕过肠道微生物群治疗癌症的替代性创新策略。因此,探索将 TAB 衍生代谢物和相关代谢信号调节用于癌症治疗的整体方法大有可为。在本综述中,我们将重点关注针对 TAB 衍生代谢物和相关代谢信号(而非细菌本身)进行癌症治疗的关键机会领域,并阐明这一新兴领域未来需要应对的挑战。
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引用次数: 0
Multiscale engineering of brain organoids for disease modeling 用于疾病建模的多尺度脑器官工程。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-27 DOI: 10.1016/j.addr.2024.115344
Cong Xu , Alia Alameri , Wei Leong , Emily Johnson , Zaozao Chen , Bin Xu , Kam W. Leong

Brain organoids hold great potential for modeling human brain development and pathogenesis. They recapitulate certain aspects of the transcriptional trajectory, cellular diversity, tissue architecture and functions of the developing brain. In this review, we explore the engineering strategies to control the molecular-, cellular- and tissue-level inputs to achieve high-fidelity brain organoids. We review the application of brain organoids in neural disorder modeling and emerging bioengineering methods to improve data collection and feature extraction at multiscale. The integration of multiscale engineering strategies and analytical methods has significant potential to advance insight into neurological disorders and accelerate drug development.

脑器官组织在模拟人类大脑发育和发病机制方面具有巨大潜力。它们再现了发育中大脑的转录轨迹、细胞多样性、组织结构和功能的某些方面。在这篇综述中,我们探讨了控制分子、细胞和组织级输入以实现高保真脑器官模型的工程策略。我们回顾了脑器官模型在神经紊乱建模中的应用,以及改进多尺度数据收集和特征提取的新兴生物工程方法。多尺度工程策略与分析方法的整合具有巨大的潜力,可促进对神经系统疾病的深入了解并加快药物开发。
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引用次数: 0
A comprehensive comparison of DNA and RNA vaccines DNA 和 RNA 疫苗的综合比较。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-27 DOI: 10.1016/j.addr.2024.115340
Chunxi Wang, Fan Yuan

Nucleic acid technology has revolutionized vaccine development, enabling rapid design and production of RNA and DNA vaccines for prevention and treatment of diseases. The successful deployment of mRNA and plasmid DNA vaccines against COVID-19 has further validated the technology. At present, mRNA platform is prevailing due to its higher efficacy, while DNA platform is undergoing rapid evolution because it possesses unique advantages that can potentially overcome the problems associated with the mRNA platform. To help understand the recent performances of the two vaccine platforms and recognize their clinical potentials in the future, this review compares the advantages and drawbacks of mRNA and DNA vaccines that are currently known in the literature, in terms of development timeline, financial cost, ease of distribution, efficacy, safety, and regulatory approval of products. Additionally, the review discusses the ongoing clinical trials, strategies for improvement, and alternative designs of RNA and DNA platforms for vaccination.

核酸技术为疫苗开发带来了革命性的变化,可快速设计和生产用于预防和治疗疾病的 RNA 和 DNA 疫苗。针对 COVID-19 的 mRNA 和质粒 DNA 疫苗的成功应用进一步验证了该技术的有效性。目前,mRNA 平台因其更高的效力而占据主导地位,而 DNA 平台则因其独特的优势有可能克服与 mRNA 平台相关的问题而正在迅速发展。为了帮助了解这两种疫苗平台的近期表现并认识到它们在未来的临床潜力,本综述从开发时间、财务成本、销售难易程度、疗效、安全性和产品的监管审批等方面比较了目前文献中已知的 mRNA 和 DNA 疫苗的优缺点。此外,该综述还讨论了正在进行的临床试验、改进策略以及用于疫苗接种的 RNA 和 DNA 平台的替代设计。
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引用次数: 0
Modulating the immune system towards a functional chronic wound healing: A biomaterials and Nanomedicine perspective 调节免疫系统,实现功能性慢性伤口愈合:生物材料与纳米医学的视角
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-24 DOI: 10.1016/j.addr.2024.115342
Kevin Las Heras , Itxaso Garcia-Orue , Fiorenza Rancan , Manoli Igartua , Edorta Santos-Vizcaino , Rosa Maria Hernandez

Chronic non-healing wounds persist as a substantial burden for healthcare systems, influenced by factors such as aging, diabetes, and obesity. In contrast to the traditionally pro-regenerative emphasis of therapies, the recognition of the immune system integral role in wound healing has significantly grown, instigating an approach shift towards immunological processes. Thus, this review explores the wound healing process, highlighting the engagement of the immune system, and delving into the behaviors of innate and adaptive immune cells in chronic wound scenarios. Moreover, the article investigates biomaterial-based strategies for the modulation of the immune system, elucidating how the adjustment of their physicochemical properties or their synergistic combination with other agents such as drugs, proteins or mesenchymal stromal cells can effectively modulate the behaviors of different immune cells. Finally this review explores various strategies based on synthetic and biological nanostructures, including extracellular vesicles, to finely tune the immune system as natural immunomodulators or therapeutic nanocarriers with promising biophysical properties.

受老龄化、糖尿病和肥胖等因素的影响,慢性伤口不愈合一直是医疗系统的沉重负担。与传统的促进再生疗法不同,人们越来越认识到免疫系统在伤口愈合中不可或缺的作用,并开始将研究方向转向免疫过程。因此,这篇综述探讨了伤口愈合过程,强调了免疫系统的参与,并深入研究了先天性和适应性免疫细胞在慢性伤口情况下的行为。此外,文章还探讨了基于生物材料的免疫系统调控策略,阐明了调整生物材料的理化特性或将其与药物、蛋白质或间充质基质细胞等其他制剂协同组合,可如何有效调控不同免疫细胞的行为。最后,本综述探讨了基于合成和生物纳米结构(包括细胞外囊泡)的各种策略,以精细调节免疫系统,使其成为具有良好生物物理特性的天然免疫调节剂或治疗性纳米载体。
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引用次数: 0
Integrating microneedles and sensing strategies for diagnostic and monitoring applications: The state of the art 整合微针和传感策略,用于诊断和监测应用:最新技术
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-24 DOI: 10.1016/j.addr.2024.115341
Shihao Pei , Samuel Babity , Ana Sara Cordeiro , Davide Brambilla

Microneedles (MNs) offer minimally-invasive access to interstitial fluid (ISF) — a potent alternative to blood in terms of monitoring physiological analytes. This property is particularly advantageous for the painless detection and monitoring of drugs and biomolecules. However, the complexity of the skin environment, coupled with the inherent nature of the analytes being detected and the inherent physical properties of MNs, pose challenges when conducting physiological monitoring using this fluid. In this review, we discuss different sensing mechanisms and highlight advancements in monitoring different targets, with a particular focus on drug monitoring. We further list the current challenges facing the field and conclude by discussing aspects of MN design which serve to enhance their performance when monitoring different classes of analytes.

微针(MNs)能以微创方式进入组织间液(ISF),这是一种替代血液监测生理分析物的有效方法。这一特性对于无痛检测和监测药物和生物分子尤为有利。然而,皮肤环境的复杂性、被检测分析物的固有性质以及 MNs 的固有物理特性,给使用这种液体进行生理监测带来了挑战。在本综述中,我们将讨论不同的传感机制,并重点介绍在监测不同目标方面取得的进展,尤其是在药物监测方面。我们进一步列举了该领域目前面临的挑战,最后讨论了 MN 设计的各个方面,这些方面有助于提高 MN 在监测不同类别分析物时的性能。
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引用次数: 0
Pathogenic fungi: Novel targets and theranostic strategies 致病真菌:新靶标和治疗策略。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-21 DOI: 10.1016/j.addr.2024.115343
Yue Wang, Linqi Wang, Chong Li
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引用次数: 0
Novel strategies for modulating the gut microbiome for cancer therapy 调节肠道微生物组以治疗癌症的新策略。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-15 DOI: 10.1016/j.addr.2024.115332
Young Seok Cho , Kai Han , Jin Xu , James J. Moon

Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.

基因组学、转录组学和代谢组学的最新进展极大地推动了我们对人类肠道微生物组及其对化疗、免疫疗法和放疗等抗癌疗法的疗效和毒性的影响的了解。特别是益生菌、益生菌和后益生菌,因其在调节肠道微生物群、维护肠道屏障和调节免疫细胞方面的独特特性而被认可,从而成为新的癌症治疗方式。然而,基于微生物疗法的临床转化仍处于早期阶段,面临着克服胃肠道的物理化学和生物学障碍、增强靶点特异性给药和提高药物生物利用度等挑战。本综述旨在强调益生菌、益生菌和后益生菌对肠道微生物组的影响及其作为癌症治疗方法的功效。此外,我们还总结了近期旨在克服口服抗癌治疗相关挑战的创新工程策略。此外,我们还将探讨工程肠道微生物组调节方法在改善免疫疗法和化疗副作用方面的潜在益处。
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引用次数: 0
Molecular probes for super-resolution imaging of drug dynamics 用于药物动态超分辨率成像的分子探针。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-10 DOI: 10.1016/j.addr.2024.115330
Hongbao Fang , Mengmeng Wang , Pengfan Wei , Qian Liu , Yan Su , Hongke Liu , Yuncong Chen , Zhi Su , Weijiang He

Super-resolution molecular probes (SRMPs) are essential tools for visualizing drug dynamics within cells, transcending the resolution limits of conventional microscopy. In this review, we provide an overview of the principles and design strategies of SRMPs, emphasizing their role in accurately tracking drug molecules. By illuminating the intricate processes of drug distribution, diffusion, uptake, and metabolism at a subcellular and molecular level, SRMPs offer crucial insights into therapeutic interventions. Additionally, we explore the practical applications of super-resolution imaging in disease treatment, highlighting the significance of SRMPs in advancing our understanding of drug action. Finally, we discuss future perspectives, envisioning potential advancements and innovations in this field. Overall, this review serves to inform and practitioners about the utility of SRMPs in driving innovation and progress in pharmacology, providing valuable insights for drug development and optimization.

超分辨率分子探针(SRMP)是观察细胞内药物动态的重要工具,它超越了传统显微镜的分辨率限制。在这篇综述中,我们将概述超分辨率分子探针的原理和设计策略,强调它们在精确追踪药物分子方面的作用。通过阐明药物在亚细胞和分子水平上分布、扩散、吸收和代谢的复杂过程,SRMP 为治疗干预提供了至关重要的见解。此外,我们还探讨了超分辨率成像在疾病治疗中的实际应用,强调了 SRMP 在促进我们了解药物作用方面的重要意义。最后,我们讨论了未来前景,展望了该领域的潜在进步和创新。总之,这篇综述旨在让从业人员了解 SRMP 在推动药理学创新和进步方面的作用,为药物开发和优化提供有价值的见解。
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引用次数: 0
Engineering antigen-presenting cells for immunotherapy of autoimmunity 工程化抗原递呈细胞用于自身免疫的免疫疗法。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-08 DOI: 10.1016/j.addr.2024.115329
Clinton T. Smith , Zhenyu Wang , Jamal S. Lewis

Autoimmune diseases are burdensome conditions that affect a significant fraction of the global population. The hallmark of autoimmune disease is a host’s immune system being licensed to attack its tissues based on specific antigens. There are no cures for autoimmune diseases. The current clinical standard for treating autoimmune diseases is the administration of immunosuppressants, which weaken the immune system and reduce auto-inflammatory responses. However, people living with autoimmune diseases are subject to toxicity, fail to mount a sufficient immune response to protect against pathogens, and are more likely to develop infections. Therefore, there is a concerted effort to develop more effective means of targeting immunomodulatory therapies to antigen-presenting cells, which are involved in modulating the immune responses to specific antigens. In this review, we highlight approaches that are currently in development to target antigen-presenting cells and improve therapeutic outcomes in autoimmune diseases.

自身免疫性疾病是一种负担沉重的疾病,影响着全球相当一部分人口。自身免疫性疾病的特征是宿主的免疫系统被授权根据特定抗原攻击其组织。目前还没有治疗自身免疫性疾病的方法。目前治疗自身免疫性疾病的临床标准是服用免疫抑制剂,这种药物会削弱免疫系统,减少自身炎症反应。然而,自身免疫性疾病患者会产生毒性,无法产生足够的免疫反应来抵御病原体,而且更容易发生感染。因此,人们正齐心协力开发更有效的方法,针对抗原递呈细胞进行免疫调节治疗,因为抗原递呈细胞参与调节对特定抗原的免疫反应。在本综述中,我们将重点介绍目前正在开发的以抗原递呈细胞为靶点、改善自身免疫性疾病治疗效果的方法。
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引用次数: 0
Immunotherapies for locally aggressive cancers 局部侵袭性癌症的免疫疗法。
IF 16.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-08 DOI: 10.1016/j.addr.2024.115331
Sarah C. Adams , Arun K. Nambiar , Eric M. Bressler , Chandrajit P. Raut , Yolonda L. Colson , Wilson W. Wong , Mark W. Grinstaff

Improving surgical resection outcomes for locally aggressive tumors is key to inducing durable locoregional disease control and preventing progression to metastatic disease. Macroscopically complete resection of the tumor is the standard of care for many cancers, including breast, ovarian, lung, sarcoma, and mesothelioma. Advancements in cancer diagnostics are increasing the number of surgically eligible cases through early detection. Thus, a unique opportunity arises to improve patient outcomes with decreased recurrence rates via intraoperative delivery treatments using local drug delivery strategies after the tumor has been resected. Of the current systemic treatments (e.g., chemotherapy, targeted therapies, and immunotherapies), immunotherapies are the latest approach to offer significant benefits. Intraoperative strategies benefit from direct access to the tumor microenvironment which improves drug uptake to the tumor and simultaneously minimizes the risk of drug entering healthy tissues thereby resulting in fewer or less toxic adverse events. We review the current state of immunotherapy development and discuss the opportunities that intraoperative treatment provides. We conclude by summarizing progress in current research, identifying areas for exploration, and discussing future prospects in sustained remission.

改善局部侵袭性肿瘤的手术切除效果是诱导持久的局部疾病控制和预防转移性疾病进展的关键。对包括乳腺癌、卵巢癌、肺癌、肉瘤和间皮瘤在内的许多癌症来说,宏观上完全切除肿瘤是治疗的标准。癌症诊断技术的进步正在通过早期检测增加符合手术条件的病例数量。因此,出现了一个独特的机会,即在切除肿瘤后,利用局部给药策略进行术中给药治疗,从而改善患者预后,降低复发率。在目前的全身治疗方法(如化疗、靶向治疗和免疫疗法)中,免疫疗法是最新的方法,可带来显著疗效。术中策略可直接进入肿瘤微环境,提高肿瘤对药物的吸收,同时将药物进入健康组织的风险降至最低,从而减少或降低毒性不良反应。我们回顾了免疫疗法的发展现状,并讨论了术中治疗带来的机遇。最后,我们总结了当前的研究进展,确定了有待探索的领域,并讨论了持续缓解的未来前景。
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引用次数: 0
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Advanced drug delivery reviews
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