Advanced drug delivery reviews最新文献_第2页

Harnessing targeted protein degradation to potentiate cancer immunotherapy: from molecular mechanisms to delivery strategies 利用靶向蛋白降解增强癌症免疫治疗：从分子机制到递送策略

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.addr.2026.115776

Ye Liu , Ihsan Ullah , Youyong Yuan , Jun Wang

Cancer immunotherapy is limited by immune escape, which is driven by overexpression of immunosuppressive proteins in the tumor microenvironment (TME). Targeted Protein Degradation (TPD) technology, utilizing cellular machinery to eliminate specific proteins, offers a powerful strategy to overcome this resistance. However, the clinical translation of TPD degraders is critically hindered by formidable delivery challenges. Their inherent physicochemical properties result in poor oral bioavailability, difficulty crossing biological barriers, rapid metabolism, and insufficient tumor accumulation, preventing effective target engagement. This review focuses on the potential of TPD technology in combination with advanced drug delivery systems (DDS) to enhance cancer immunotherapy. We elaborate on how TPD reshapes the TME by degrading key immunomodulatory targets. Critically, this review provides an in-depth analysis of the major delivery bottlenecks currently limiting the efficacy of TPD degraders. Furthermore, it introduces advanced delivery strategies designed to overcome these obstacles, including nanocarriers, hydrogels, microneedles, and various stimuli-responsive delivery systems. Successfully overcoming these delivery obstacles is vital to unlocking the full therapeutic efficacy of TPD. Such progress holds promises for reprogramming immunosuppressive TME, overcoming resistance to existing immunotherapies, broadening the population of patients responsive to treatment, and ultimately delivering durable clinical benefits to more cancer patients.

肿瘤免疫治疗受到免疫逃逸的限制，免疫逃逸是由肿瘤微环境（TME）中免疫抑制蛋白过度表达驱动的。靶向蛋白质降解（TPD）技术，利用细胞机制来消除特定的蛋白质，提供了一个强大的策略来克服这种阻力。然而，TPD降解物的临床转化受到递送挑战的严重阻碍。其固有的物理化学性质导致口服生物利用度差，难以跨越生物屏障，代谢快，肿瘤蓄积不足，阻碍了有效的靶标结合。本文综述了TPD技术与先进的药物输送系统（DDS）结合在增强癌症免疫治疗中的潜力。我们详细阐述了TPD如何通过降解关键的免疫调节靶点来重塑TME。重要的是，这篇综述深入分析了目前限制TPD降解剂功效的主要递送瓶颈。此外，它还介绍了旨在克服这些障碍的先进递送策略，包括纳米载体、水凝胶、微针和各种刺激响应递送系统。成功克服这些递送障碍对于释放TPD的全部治疗效果至关重要。这一进展有望对免疫抑制性TME进行重编程，克服对现有免疫疗法的耐药性，扩大对治疗有反应的患者群体，并最终为更多癌症患者带来持久的临床益处。

{"title":"Harnessing targeted protein degradation to potentiate cancer immunotherapy: from molecular mechanisms to delivery strategies","authors":"Ye Liu , Ihsan Ullah , Youyong Yuan , Jun Wang","doi":"10.1016/j.addr.2026.115776","DOIUrl":"10.1016/j.addr.2026.115776","url":null,"abstract":"<div><div>Cancer immunotherapy is limited by immune escape, which is driven by overexpression of immunosuppressive proteins in the tumor microenvironment (TME). Targeted Protein Degradation (TPD) technology, utilizing cellular machinery to eliminate specific proteins, offers a powerful strategy to overcome this resistance. However, the clinical translation of TPD degraders is critically hindered by formidable delivery challenges. Their inherent physicochemical properties result in poor oral bioavailability, difficulty crossing biological barriers, rapid metabolism, and insufficient tumor accumulation, preventing effective target engagement. This review focuses on the potential of TPD technology in combination with advanced drug delivery systems (DDS) to enhance cancer immunotherapy. We elaborate on how TPD reshapes the TME by degrading key immunomodulatory targets. Critically, this review provides an in-depth analysis of the major delivery bottlenecks currently limiting the efficacy of TPD degraders. Furthermore, it introduces advanced delivery strategies designed to overcome these obstacles, including nanocarriers, hydrogels, microneedles, and various stimuli-responsive delivery systems. Successfully overcoming these delivery obstacles is vital to unlocking the full therapeutic efficacy of TPD. Such progress holds promises for reprogramming immunosuppressive TME, overcoming resistance to existing immunotherapies, broadening the population of patients responsive to treatment, and ultimately delivering durable clinical benefits to more cancer patients.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115776"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Medicinal gases for treating central nervous system injuries 用于治疗中枢神经系统损伤的医用气体

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.addr.2026.115782

Rebecca I. Sienel , Nikolaus Plesnila

Central nervous system (CNS) injuries—such as stroke, traumatic brain injury, and perinatal hypoxia—trigger complex secondary cascades involving oxidative stress, inflammation, and apoptosis that limit recovery and therapeutic efficacy. Recent advances in medical gas delivery offer a novel, multifaceted approach to modulate these pathological processes. Gases including hydrogen, nitric oxide, carbon monoxide, xenon, and argon demonstrate potent neuroprotective, anti-inflammatory, and vasomodulatory properties in preclinical models. This review synthesizes current evidence on gas-based interventions across CNS pathologies, elucidates their molecular mechanisms, and evaluates translational challenges related to timing, dosing, and delivery technologies. Gas therapeutics represent a promising frontier in neurocritical care with potential to transform outcomes in otherwise intractable neurological injuries.

中枢神经系统（CNS）损伤，如中风、外伤性脑损伤和围产期缺氧，可触发复杂的次级级联反应，包括氧化应激、炎症和细胞凋亡，从而限制恢复和治疗效果。最近在医疗气体输送提供了一个新的，多方面的方法来调节这些病理过程。包括氢气、一氧化氮、一氧化碳、氙和氩气在内的气体在临床前模型中显示出有效的神经保护、抗炎和血管调节特性。这篇综述综合了目前针对中枢神经系统病理的气体干预的证据，阐明了它们的分子机制，并评估了与时间、剂量和递送技术相关的转化挑战。气体疗法代表了神经危重症护理的一个有前途的前沿，有可能改变其他顽固性神经损伤的结果。

引用次数: 0

Editorial: Novel ultrasound-based strategies for precision therapeutics and visualization 编辑：新的基于超声的精确治疗和可视化策略。

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2025-12-16 DOI: 10.1016/j.addr.2025.115763

Xinwu Cui , Xiaoyuan Chen

引用次数: 0

Covalent chemistry in targeted protein degradation 靶向蛋白降解中的共价化学

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-12 DOI: 10.1016/j.addr.2026.115777

Jing Tan , Yuxin Liang , Shiqun Shao , Youqing Shen

Targeted protein degradation (TPD) has revolutionized drug discovery by enabling the selective removal of specific proteins within and outside cells through the cell’s natural degradation pathways. While various TPD modalities have demonstrated immense promise, the integration of covalent chemistry is rapidly emerging as a crucial approach to enhance target engagement, improve selectivity, and overcome limitations associated with non-covalent interactions. This review provides a comprehensive overview of the current landscape of covalent TPD and systematically explores how covalent chemistry advances the field of TPD. We first detail the diverse covalent modification strategies, reactive amino acid residues, and electrophilic warheads employed in the design of covalent ligands. Next, we discuss methodologies for covalent ligand discovery, including ligand-first and electrophile-first approaches. Finally, we highlight specific examples of covalent degraders across different TPD modalities, emphasizing their mechanisms of action and therapeutic potential. By integrating current knowledge and future directions, this review aims to provide insights for the rational design of next-generation covalent degraders and underscore their implications for the future of drug discovery.

靶向蛋白质降解（TPD）通过细胞的自然降解途径选择性去除细胞内外的特定蛋白质，从而彻底改变了药物的发现。虽然各种TPD模式已经显示出巨大的前景，但共价化学的整合正迅速成为增强靶标结合、提高选择性和克服非共价相互作用局限性的关键方法。本文综述了共价TPD的现状，并系统地探讨了共价化学如何推动TPD领域的发展。我们首先详细介绍了各种共价修饰策略、活性氨基酸残基和共价配体设计中使用的亲电弹头。接下来，我们讨论共价配体的发现方法，包括配体优先和亲电优先方法。最后，我们强调了共价降解物在不同TPD模式中的具体例子，强调了它们的作用机制和治疗潜力。通过整合现有知识和未来方向，本文旨在为下一代共价降解物的合理设计提供见解，并强调其对未来药物发现的意义。

{"title":"Covalent chemistry in targeted protein degradation","authors":"Jing Tan , Yuxin Liang , Shiqun Shao , Youqing Shen","doi":"10.1016/j.addr.2026.115777","DOIUrl":"10.1016/j.addr.2026.115777","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) has revolutionized drug discovery by enabling the selective removal of specific proteins within and outside cells through the cell’s natural degradation pathways. While various TPD modalities have demonstrated immense promise, the integration of covalent chemistry is rapidly emerging as a crucial approach to enhance target engagement, improve selectivity, and overcome limitations associated with non-covalent interactions. This review provides a comprehensive overview of the current landscape of covalent TPD and systematically explores how covalent chemistry advances the field of TPD. We first detail the diverse covalent modification strategies, reactive amino acid residues, and electrophilic warheads employed in the design of covalent ligands. Next, we discuss methodologies for covalent ligand discovery, including ligand-first and electrophile-first approaches. Finally, we highlight specific examples of covalent degraders across different TPD modalities, emphasizing their mechanisms of action and therapeutic potential. By integrating current knowledge and future directions, this review aims to provide insights for the rational design of next-generation covalent degraders and underscore their implications for the future of drug discovery.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115777"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optical imaging and spectroscopic characterization of subvisible particles in protein therapeutics 蛋白质治疗中亚可见粒子的光学成像和光谱表征。

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.addr.2026.115779

Brian S. Wong , Jing Ling , Yongchao Su , Dan Fu

The presence of subvisible particles in protein-based pharmaceutics is a critical quality attribute that is highly regulated due to potential risks to product stability, quality, bioavailability, and patient safety. While numerous analytical technologies have been developed to measure and analyze these particles, optical characterization methods are widely used for their simplicity, robustness, and versatility. Selecting the appropriate technique from a vast array of optical spectroscopy and imaging methods can be overwhelming, but it is crucial for successful characterization. For example, compendial methods such as light obscuration are most commonly used but can underestimate particle counts and are unable to provide chemical identification. This review article aims to provide a comprehensive comparison of optical particle characterization techniques, detailing their physical principles, applications, strengths, and weaknesses. We evaluate methods based on elastic light scattering, flow-based imaging, particle tracking, and vibrational spectroscopy. We highlight the inherent trade-off between analytical throughput and information content, aiming to guide the rational selection of analytical tools for the comprehensive characterization of subvisible particles in protein therapeutics.

蛋白类药物中不可见颗粒的存在是一个关键的质量属性，由于对产品稳定性、质量、生物利用度和患者安全存在潜在风险，因此受到高度监管。虽然已经开发了许多分析技术来测量和分析这些颗粒，但光学表征方法因其简单，稳健性和通用性而被广泛使用。从大量的光谱学和成像方法中选择合适的技术可能是压倒性的，但它对于成功表征至关重要。例如，最常用的药典方法是光遮挡，但可能低估颗粒计数，无法提供化学鉴定。本文旨在对光学粒子表征技术进行全面比较，详细介绍其物理原理、应用、优缺点。我们评估了基于弹性光散射、流成像、粒子跟踪和振动光谱的方法。我们强调分析吞吐量和信息内容之间的内在权衡，旨在指导合理选择分析工具，以全面表征蛋白质治疗中不可见颗粒的特征。

{"title":"Optical imaging and spectroscopic characterization of subvisible particles in protein therapeutics","authors":"Brian S. Wong , Jing Ling , Yongchao Su , Dan Fu","doi":"10.1016/j.addr.2026.115779","DOIUrl":"10.1016/j.addr.2026.115779","url":null,"abstract":"<div><div>The presence of subvisible particles in protein-based pharmaceutics is a critical quality attribute that is highly regulated due to potential risks to product stability, quality, bioavailability, and patient safety. While numerous analytical technologies have been developed to measure and analyze these particles, optical characterization methods are widely used for their simplicity, robustness, and versatility. Selecting the appropriate technique from a vast array of optical spectroscopy and imaging methods can be overwhelming, but it is crucial for successful characterization. For example, compendial methods such as light obscuration are most commonly used but can underestimate particle counts and are unable to provide chemical identification. This review article aims to provide a comprehensive comparison of optical particle characterization techniques, detailing their physical principles, applications, strengths, and weaknesses. We evaluate methods based on elastic light scattering, flow-based imaging, particle tracking, and vibrational spectroscopy. We highlight the inherent trade-off between analytical throughput and information content, aiming to guide the rational selection of analytical tools for the comprehensive characterization of subvisible particles in protein therapeutics.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115779"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The predictive edge: modeling and simulation in drug product development 预测优势：药品开发中的建模和仿真

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-25 DOI: 10.1016/j.addr.2026.115784

Sanjay Konagurthu , Dineli T.S. Ranathunga , Stephanie Buchanan , Nairuti Milan Mehta , Tom Reynolds

It is well-known that drug development is challenging and a time- and resource-intensive endeavor. Historically, it has relied heavily on trial-and-error, empirical approaches that yield a low probability of success. Despite continuous efforts to improve efficiency across the development stages the overall success rate from clinical trial initiation to market approval remains low. In response to these challenges, in-silico predictive modeling and simulations are becoming indispensable tools for accelerating and de-risking the drug product development process. These computational methods use simulated and real-world data to guide decision-making across the entire development pipeline. Notably, these tools are now gaining widespread acceptance not only in discovery but also across the delivery and formulation stages of drug development. Advances in artificial intelligence (AI) and machine learning (ML) are proving transformative, enabling rapid analysis of large datasets and the development of predictive models that enhance classification, prediction, and optimization capabilities across the drug product development process. This review provides an overview of the various in-silico predictive modeling and simulation techniques for drug product development, emphasizing the use of AI/ML, and their applications in drug delivery. We highlight their role in improving drug performance, manufacturability, stability, safety, and overall success from clinical development through commercialization.

众所周知，药物开发具有挑战性，是一项耗时和资源密集的工作。从历史上看，它严重依赖于试错和经验方法，成功的可能性很低。尽管不断努力提高整个开发阶段的效率，但从临床试验开始到市场批准的总体成功率仍然很低。为了应对这些挑战，计算机预测建模和模拟正在成为加速和降低药物产品开发过程风险的不可或缺的工具。这些计算方法使用模拟和真实世界的数据来指导整个开发管道中的决策。值得注意的是，这些工具现在不仅在发现方面，而且在药物开发的整个交付和配制阶段都得到了广泛的接受。人工智能（AI）和机器学习（ML）的进步正在被证明具有变革性，能够快速分析大型数据集并开发预测模型，从而增强整个药品开发过程中的分类、预测和优化能力。本文综述了用于药物产品开发的各种计算机预测建模和仿真技术，重点介绍了AI/ML的使用及其在药物传递中的应用。我们强调它们在改善药物性能、可制造性、稳定性、安全性以及从临床开发到商业化的整体成功方面的作用。

{"title":"The predictive edge: modeling and simulation in drug product development","authors":"Sanjay Konagurthu , Dineli T.S. Ranathunga , Stephanie Buchanan , Nairuti Milan Mehta , Tom Reynolds","doi":"10.1016/j.addr.2026.115784","DOIUrl":"10.1016/j.addr.2026.115784","url":null,"abstract":"<div><div>It is well-known that drug development is challenging and a time- and resource-intensive endeavor. Historically, it has relied heavily on trial-and-error, empirical approaches that yield a low probability of success. Despite continuous efforts to improve efficiency across the development stages the overall success rate from clinical trial initiation to market approval remains low. In response to these challenges, in-silico predictive modeling and simulations are becoming indispensable tools for accelerating and de-risking the drug product development process. These computational methods use simulated and real-world data to guide decision-making across the entire development pipeline. Notably, these tools are now gaining widespread acceptance not only in discovery but also across the delivery and formulation stages of drug development. Advances in artificial intelligence (AI) and machine learning (ML) are proving transformative, enabling rapid analysis of large datasets and the development of predictive models that enhance classification, prediction, and optimization capabilities across the drug product development process. This review provides an overview of the various in-silico predictive modeling and simulation techniques for drug product development, emphasizing the use of AI/ML, and their applications in drug delivery. We highlight their role in improving drug performance, manufacturability, stability, safety, and overall success from clinical development through commercialization.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115784"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic engineering approaches in stem and somatic cells for the generation of insulin-producing β-cells 干细胞和体细胞中产生胰岛素生成β细胞的基因工程方法

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.addr.2025.115766

Abiramy Jeyagaran , Katja Schenke-Layland

Cell replacement therapies hold great promise for the treatment of type 1 diabetes mellitus; however, the obtaining of sufficient transplantable β-cells limits the availability of this treatment option. The generation of β-cells from human pluripotent stem cells or other somatic cells through classical differentiation, forward programming, or transdifferentiation approaches offers an alternative source of therapeutic β-cells for the treatment of type 1 diabetes mellitus. Through increasing understanding of pancreatic and β-cell development, transcription factors neurogenin 3 (NGN3), pancreas/duodenum homeobox protein 1 (PDX1), and MAF BZIP Transcription Factor A (MAFA) have been identified to be crucial for glucose-responsive insulin secretion of adult β-cells. In this review, we address and discuss recent advances in transdifferentiation approaches using these three markers for the timely generation of mature β-cells, and the insights they provide on cell development and plasticity.

细胞替代疗法对治疗1型糖尿病有很大的希望；然而，获得足够的可移植β细胞限制了这种治疗选择的可用性。通过经典分化、正向编程或转分化方法，从人类多能干细胞或其他体细胞中产生β细胞，为治疗1型糖尿病提供了另一种治疗性β细胞来源。随着对胰腺和β细胞发育的进一步了解，转录因子神经原素3 （NGN3）、胰腺/十二指肠同源盒蛋白1 （PDX1）和MAF BZIP转录因子A （MAFA）已被确定对成人β细胞的葡萄糖反应性胰岛素分泌至关重要。在这篇综述中，我们讨论了利用这三种标记及时生成成熟β细胞的转分化方法的最新进展，以及它们对细胞发育和可塑性提供的见解。

引用次数: 0

Technology for Nucleic Acid Delivery in the Treatment of Hematological Malignancies 核酸输送技术在血液系统恶性肿瘤治疗中的应用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-16 DOI: 10.1016/j.addr.2026.115780

Saba Abbasi Dezfouli , Hasan Uludağ , Mohammad Nasrullah , Amarnath Praphakar Rajendran , Remant K.C.

Blood (hematological) cancers display a wide spectrum of etiologies that can be attributed to specific molecular and chromosomal changes. While the uncontrolled proliferation of blood cells could be controlled to some degree by conventional anti-neoplastic agents, advanced therapies are needed to enhance the chances of survival. Nucleic acid therapeutics offer a great promise in combating blood cancers; they could be tailored to address the root cause of the diseases and can be deployed on their own or in combination with clinical drugs to achieve superior outcomes. In this review, we summarize the technology of delivering nucleic acids for the treatment of blood cancers. We start with the review of common types of hematological malignancies, highlighting the molecular pathology behind the malignancies. We then articulate the spectrum of nucleic acids promising for therapy as well as their critical features for delivery and securing efficacious outcomes. Since it is well recognized that the critical challenge is deploying nucleic acids safely in a clinical setting, we focus on the more-predictable, leading synthetic carriers promising for delivery of nucleic acids in clinics. We emphasize synthetic carriers that form supramolecular complexes with nucleic acids, resulting in nanoparticulate formulations, as well as approaches to derivatize the nucleic acids to make them suitable for cellular uptake and targeted delivery. We then summarize highly promising attempts to tackle blood cancers using new approaches, emphasizing microRNA-mediated gene regulation and the CRISPR-based gene editing approaches. These new approaches are interrogated especially from the perspective of delivery technology, with the purpose of designing improved delivery systems. We conclude with the authors' perspective on the future of nucleic acid therapeutics for the treatment of blood cancers, providing authors' perspectives for significant advances in the field.

血液（血液学）癌症表现出广泛的病因，可归因于特定的分子和染色体变化。虽然传统的抗肿瘤药物可以在一定程度上控制血细胞的不受控制的增殖，但需要先进的治疗方法来提高生存的机会。核酸疗法为对抗血癌提供了巨大的希望；它们可以针对疾病的根本原因进行定制，可以单独使用或与临床药物联合使用，以取得更好的效果。本文就核酸输送技术在血癌治疗中的应用作一综述。我们首先回顾常见类型的恶性血液病，强调恶性肿瘤背后的分子病理学。然后，我们阐明了有望用于治疗的核酸谱，以及它们的关键特征，以提供和确保有效的结果。众所周知，关键的挑战是在临床环境中安全地部署核酸，因此我们将重点放在更可预测的、有希望在临床中递送核酸的领先合成载体上。我们强调与核酸形成超分子复合物的合成载体，从而产生纳米颗粒配方，以及使核酸衍生化以使其适合细胞摄取和靶向递送的方法。然后，我们总结了使用新方法治疗血癌的极有希望的尝试，强调了微rna介导的基因调控和基于crispr的基因编辑方法。这些新方法特别从交付技术的角度进行了探讨，目的是设计改进的交付系统。我们总结了作者对核酸疗法治疗血癌的未来的看法，为该领域的重大进展提供了作者的观点。

{"title":"Technology for Nucleic Acid Delivery in the Treatment of Hematological Malignancies","authors":"Saba Abbasi Dezfouli , Hasan Uludağ , Mohammad Nasrullah , Amarnath Praphakar Rajendran , Remant K.C.","doi":"10.1016/j.addr.2026.115780","DOIUrl":"10.1016/j.addr.2026.115780","url":null,"abstract":"<div><div>Blood (hematological) cancers display a wide spectrum of etiologies that can be attributed to specific molecular and chromosomal changes. While the uncontrolled proliferation of blood cells could be controlled to some degree by conventional anti-neoplastic agents, advanced therapies are needed to enhance the chances of survival. Nucleic acid therapeutics offer a great promise in combating blood cancers; they could be tailored to address the root cause of the diseases and can be deployed on their own or in combination with clinical drugs to achieve superior outcomes. In this review, we summarize the technology of delivering nucleic acids for the treatment of blood cancers. We start with the review of common types of hematological malignancies, highlighting the molecular pathology behind the malignancies. We then articulate the spectrum of nucleic acids promising for therapy as well as their critical features for delivery and securing efficacious outcomes. Since it is well recognized that the critical challenge is deploying nucleic acids safely in a clinical setting, we focus on the more-predictable, leading synthetic carriers promising for delivery of nucleic acids in clinics. We emphasize synthetic carriers that form supramolecular complexes with nucleic acids, resulting in nanoparticulate formulations, as well as approaches to derivatize the nucleic acids to make them suitable for cellular uptake and targeted delivery. We then summarize highly promising attempts to tackle blood cancers using new approaches, emphasizing microRNA-mediated gene regulation and the CRISPR-based gene editing approaches. These new approaches are interrogated especially from the perspective of delivery technology, with the purpose of designing improved delivery systems. We conclude with the authors' perspective on the future of nucleic acid therapeutics for the treatment of blood cancers, providing authors' perspectives for significant advances in the field.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115780"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergies between data science methods and innovative drug delivery technologies 数据科学方法和创新给药技术之间的协同作用

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.addr.2026.115783

David A. Winkler

Most areas of science and technology and beyond are undergoing an almost unprecedented rate of change, driven largely by the rapid growth in automation and robotics, computational power, and AI and machine learning algorithms. Many areas of science and medicine have adopted these technologies or are on a steep learning curve to do so in the short to medium term. Drug delivery systems that are very important for optimising therapeutic efficacy, patient compliance, and amelioration of side-effects are similarly undergoing a quiet revolution in modalities. However, drug delivery systems are arguably lagging many other scientific and biomedical fields in applying informatics, physics-based computational design and simulation approaches, and AI and machine learning to design, optimisation, and simulation of drug delivery systems. Here I review studies in which selected computational methods have been employed for these purposes, aiming to highlight their potential to accelerate the provision of more effective drug delivery systems and to identify modalities in which the benefits of these computational methods have not been achieved at all, or at least sub-optimally. The aim is to focus on less well-addressed existing and emerging drug delivery systems and to provide a perspective on what needs to be done, what could be done better, and where the synergistic partnership between computational/AI methods and contemporary drug delivery system may lead in the future.

大多数科学和技术领域以及其他领域正在经历一场几乎前所未有的变革，这主要是由自动化和机器人技术、计算能力、人工智能和机器学习算法的快速增长所推动的。科学和医学的许多领域已经采用了这些技术，或者在短期到中期正处于陡峭的学习曲线上。对于优化治疗效果、患者依从性和改善副作用非常重要的药物输送系统同样正在经历一场静悄悄的模式革命。然而，药物输送系统在应用信息学、基于物理的计算设计和模拟方法以及人工智能和机器学习来设计、优化和模拟药物输送系统方面，可以说落后于许多其他科学和生物医学领域。在这里，我回顾了一些研究，其中选定的计算方法已被用于这些目的，旨在强调它们加速提供更有效的药物输送系统的潜力，并确定这些计算方法的好处根本没有实现的模式，或者至少是次优的。其目的是将重点放在现有的和新兴的药物输送系统上，并就需要做什么、可以做得更好以及计算/人工智能方法与当代药物输送系统之间的协同伙伴关系在未来可能导致的情况提供一个视角。

{"title":"Synergies between data science methods and innovative drug delivery technologies","authors":"David A. Winkler","doi":"10.1016/j.addr.2026.115783","DOIUrl":"10.1016/j.addr.2026.115783","url":null,"abstract":"<div><div>Most areas of science and technology and beyond are undergoing an almost unprecedented rate of change, driven largely by the rapid growth in automation and robotics, computational power, and AI and machine learning algorithms. Many areas of science and medicine have adopted these technologies or are on a steep learning curve to do so in the short to medium term. Drug delivery systems that are very important for optimising therapeutic efficacy, patient compliance, and amelioration of side-effects are similarly undergoing a quiet revolution in modalities. However, drug delivery systems are arguably lagging many other scientific and biomedical fields in applying informatics, physics-based computational design and simulation approaches, and AI and machine learning to design, optimisation, and simulation of drug delivery systems. Here I review studies in which selected computational methods have been employed for these purposes, aiming to highlight their potential to accelerate the provision of more effective drug delivery systems and to identify modalities in which the benefits of these computational methods have not been achieved at all, or at least sub-optimally. The aim is to focus on less well-addressed existing and emerging drug delivery systems and to provide a perspective on what needs to be done, what could be done better, and where the synergistic partnership between computational/AI methods and contemporary drug delivery system may lead in the future.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115783"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic gases as emerging treatments for oral diseases 治疗气体作为口腔疾病的新疗法

IF 17.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews

Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.addr.2026.115774

Ann Badia , Jihyuk Yang , Sara Aliyeva , Yonghyun Choi , Jonghoon Choi , Tagbo H.R. Niepa

Oral delivery of gas-based therapies provides a targeted, minimally invasive approach to treating oral diseases. Conventional strategies, such as mechanical debridement, antibiotics, and surgical intervention, are limited by the inaccessibility of oral biofilms, the development of antimicrobial resistance, and challenges in promoting tissue regeneration. Therapeutic gases, including oxygen (O₂), ozone (O₃), nitrous oxide (N₂O), nitric oxide (NO), carbon monoxide (CO), carbon dioxide (CO₂), hydrogen (H₂), hydrogen sulfide (H₂S), and argon-based plasma, have emerged as promising options to address these challenges. Each gas exhibits distinct biological effects relevant to dental care, including antimicrobial properties, promotion of tissue healing and regeneration via angiogenesis and collagen synthesis, and anti-inflammatory benefits through modulation of oxidative stress and immune responses. Despite these advantages, significant barriers hinder clinical translation, such as dose control, toxicity at high concentrations, delivery limitations, and the high cost of specialized equipment. To address these challenges, research is advancing innovative delivery systems, such as gas-generating nanoplatforms, hydrogels, capsules, and nano-bubble water, that enable responsive release of the therapeutic gases within the oral environment. Future directions include developing safe, patient-friendly delivery technologies, expanding clinical trials, and establishing a transparent regulatory framework to fully realize the potential of gas-based therapies as effective adjuncts or alternatives to conventional dental treatments.

口服气体疗法为治疗口腔疾病提供了一种靶向性、微创性的方法。传统的策略，如机械清创、抗生素和手术干预，受到口腔生物膜难以接近、抗菌素耐药性的发展以及促进组织再生的挑战的限制。治疗气体，包括氧气（O2）、臭氧（O3）、氧化亚氮（N2O）、一氧化氮（NO）、一氧化碳（CO）、二氧化碳（CO2）、氢气（H2）、硫化氢（H2S）和氩基等离子体，已经成为解决这些挑战的有希望的选择。每种气体都表现出与牙科保健相关的不同生物效应，包括抗菌特性、通过血管生成和胶原合成促进组织愈合和再生，以及通过调节氧化应激和免疫反应而具有抗炎作用。尽管有这些优势，但临床转化仍存在重大障碍，如剂量控制、高浓度毒性、给药限制和专用设备的高成本。为了应对这些挑战，研究人员正在推进创新的输送系统，如产生气体的纳米平台、水凝胶、胶囊和纳米气泡水，这些系统能够在口腔环境中响应性地释放治疗气体。未来的发展方向包括开发安全、对患者友好的输送技术，扩大临床试验，建立透明的监管框架，以充分实现气体疗法作为传统牙科治疗的有效辅助或替代方案的潜力。

{"title":"Therapeutic gases as emerging treatments for oral diseases","authors":"Ann Badia , Jihyuk Yang , Sara Aliyeva , Yonghyun Choi , Jonghoon Choi , Tagbo H.R. Niepa","doi":"10.1016/j.addr.2026.115774","DOIUrl":"10.1016/j.addr.2026.115774","url":null,"abstract":"<div><div>Oral delivery of gas-based therapies provides a targeted, minimally invasive approach to treating oral diseases. Conventional strategies, such as mechanical debridement, antibiotics, and surgical intervention, are limited by the inaccessibility of oral biofilms, the development of antimicrobial resistance, and challenges in promoting tissue regeneration. Therapeutic gases, including oxygen (O<sub>2</sub>), ozone (O<sub>3</sub>), nitrous oxide (N<sub>2</sub>O), nitric oxide (NO), carbon monoxide (CO), carbon dioxide (CO<sub>2</sub>), hydrogen (H<sub>2</sub>), hydrogen sulfide (H<sub>2</sub>S), and argon-based plasma, have emerged as promising options to address these challenges. Each gas exhibits distinct biological effects relevant to dental care, including antimicrobial properties, promotion of tissue healing and regeneration via angiogenesis and collagen synthesis, and anti-inflammatory benefits through modulation of oxidative stress and immune responses. Despite these advantages, significant barriers hinder clinical translation, such as dose control, toxicity at high concentrations, delivery limitations, and the high cost of specialized equipment. To address these challenges, research is advancing innovative delivery systems, such as gas-generating nanoplatforms, hydrogels, capsules, and nano-bubble water, that enable responsive release of the therapeutic gases within the oral environment. Future directions include developing safe, patient-friendly delivery technologies, expanding clinical trials, and establishing a transparent regulatory framework to fully realize the potential of gas-based therapies as effective adjuncts or alternatives to conventional dental treatments.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115774"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0