Advanced drug delivery reviews最新文献_第2页

Rational modification of PROTACs for tumor-selective protein degradation 合理修饰PROTACs用于肿瘤选择性蛋白降解

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.addr.2026.115775

Zhongliang Fu , Meichen Pan , Chunrong Yang , Hongwei Hou , Jinghong Li

{"title":"Rational modification of PROTACs for tumor-selective protein degradation","authors":"Zhongliang Fu , Meichen Pan , Chunrong Yang , Hongwei Hou , Jinghong Li","doi":"10.1016/j.addr.2026.115775","DOIUrl":"10.1016/j.addr.2026.115775","url":null,"abstract":"<div><div>Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that hijack the ubiquitin-proteasome system to catalytically degrade pathogenic proteins. With the ability to target “undruggable” proteins and exert sustained pharmacological effects, PROTACs hold considerable promise for cancer therapy. However, achieving tumor-selective protein degradation remains a central challenge. This review outlines the application of PROTACs in cancer treatment and systematically summarizes emerging strategies to enhance tumor specificity. These approaches leverage hallmark features of tumors, distinctive surface biomarkers and a unique tumor microenvironment (TME), and are broadly categorized into two classes: active targeting, which employs tumor-selective ligands to enrich PROTACs in malignant cells; and conditionally activated strategies, where TME cues either selectively trigger PROTAC prodrugs or induce structural transformations in nanocarriers to enhance drug accumulation at the tumor site. By elucidating these mechanisms, we aim to bridge medicinal chemistry and intelligent nanomedicine, underpinning the tumor-selective protein degradation strategies and offering perspectives on future research directions to improve the biodistribution, safety, and therapeutic efficacy of next-generation PROTACs.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115775"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949886","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

Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease 生物制剂-器械组合：延长后段眼病的治疗时间

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.addr.2026.115773

Shuqian Zhu , Jianjun Zhang , Xuling Jiang , Cheng Peng , Huiqin Liu , Feng Qian

{"title":"Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease","authors":"Shuqian Zhu , Jianjun Zhang , Xuling Jiang , Cheng Peng , Huiqin Liu , Feng Qian","doi":"10.1016/j.addr.2026.115773","DOIUrl":"10.1016/j.addr.2026.115773","url":null,"abstract":"<div><div>Posterior segment ocular diseases (e.g., age-related macular degeneration and diabetic retinopathy, etc.) often necessitate frequent intravitreal (IVT) injections of biologics, due to the rapid drug clearance and formidable ocular barriers. While molecular engineering strategies and high-concentration protein formulations could extend the administration intervals to a certain extent, they are confronted with critical challenges, protein aggregation, high viscosity, and limited duration. This has spurred the development of innovative biologics-device combination products, which represent a paradigm shift towards prolonged therapy. This comprehensive review examines the latest advancements of these combination platforms, including refillable implants (e.g., SUSVIMO®), encapsulated cell technology (e.g., ENCELTO™), and recombinant adeno-associated virus (rAAV) vectors (e.g., LUXTURNA®). The progress in biologics - device combination technologies has significantly reduced the frequency of ocular injections. However, substantial hurdles, such as instability caused by material-biologics interactions, potential risks during the sterilization and manufacturing processes, safety risks, and the evolving regulatory landscape, still need to be addressed. Achieving a balance between the stability of biologics and advanced device design, enhancing long-term safety, and developing responsive smart systems with real-time monitoring and feedback capabilities remain crucial for the advancement of next-generation ophthalmic therapies.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115773"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920277","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

Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system 用于改善向中枢神经系统递送寡核苷酸疗法的生物偶联物

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-03-01 Epub Date: 2026-01-15 DOI: 10.1016/j.addr.2026.115778

Hye Jin Lee , Yunxuan Xie , Colin F. Greineder , Peter M. Tessier

{"title":"Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system","authors":"Hye Jin Lee , Yunxuan Xie , Colin F. Greineder , Peter M. Tessier","doi":"10.1016/j.addr.2026.115778","DOIUrl":"10.1016/j.addr.2026.115778","url":null,"abstract":"<div><div>Oligonucleotide therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), have gained increasing attention as a novel modality for gene-targeted interventions for central nervous system (CNS) disorders, particularly in the context of rare and inherited neurological conditions. By correcting pathogenic abnormalities in gene splicing or expression, oligonucleotide therapeutics offer a combination of extreme specificity and disease-modifying or even curative effects. However, achieving robust delivery to the CNS after systemic administration remains a significant challenge due to the presence of the blood-brain barrier and the intrinsic physicochemical limitations of oligonucleotide therapeutics, such as their large molecular size, high charge, and susceptibility to enzymatic degradation. Peptide-, antibody-, and lipid-based conjugates have emerged as versatile strategies for CNS oligonucleotide delivery, offering distinct advantages in molecular recognition, tunability, biocompatibility, and structural uniformity. Here, we review emerging design principles for engineering peptide, antibody, and lipid conjugates to enhance binding affinity, target selectivity, pharmacokinetics, and pharmacodynamics of oligonucleotide therapeutics for CNS applications. We also discuss how engineered delivery platforms have the potential to improve therapeutic efficacy across a spectrum of neurological disorders, from rare hereditary syndromes to highly prevalent neurodegenerative diseases.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"230 ","pages":"Article 115778"},"PeriodicalIF":17.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993315","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

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