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

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

{"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

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

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

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

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

{"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

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

{"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

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

{"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

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

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

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.

{"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

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

David A. Winkler

{"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

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

{"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