Advanced drug delivery reviews最新文献

Bioorthogonal chemistry conjugates: ADCs and beyond. 生物正交化学偶联物：adc及其他。

IF 21 1区医学

Advanced drug delivery reviews Pub Date : 2026-10-19 DOI: 10.1016/j.addr.2026.115979

Bonnie Long, Shawn C Owen

{"title":"Bioorthogonal chemistry conjugates: ADCs and beyond.","authors":"Bonnie Long, Shawn C Owen","doi":"10.1016/j.addr.2026.115979","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115979","url":null,"abstract":"<p><p>Bioorthogonal click chemistry has played a transformative role in developing advanced hybrid conjugates. These molecular constructs are formed by chemically linking a targeting component to a functional moiety through a suitable linker. Therapeutic conjugates are designed to deliver a biologically active agent to a specific target to treat, prevent, or modify a disease process. By directing the payload to a defined site of action, these conjugates can improve efficacy while reducing off-target effects and systemic toxicity. Among these, antibody-drug conjugates stand out as the most clinically successful compounds. Where various chemical strategies, such as thiol-maleimide additions and site-selective glycan engineering, are employed to attach toxic payloads to antibodies with high precision and reduced sample heterogeneity. Beyond delivery of potent therapeutic payloads, click chemistry approaches have expanded into radioimmunoconjugates for diagnostics, oligonucleotide conjugates for gene silencing, and the creation of bispecific antibodies that can target multiple disease pathways simultaneously. These modular approaches often utilize combinations of ligation and chemical conjugation to preserve the structural integrity and immune functions of the original proteins. These techniques are now being applied to modulate living systems, including cell surface engineering, where metabolic machinery is exploited to install chemical handles on living cells for therapeutic tracking and \"click-to-release\" drug activation in vivo. Ultimately, current and emerging molecular \"click\" technologies emphasize a shift toward homogeneous, site-specific methods that expand the functionality and improve the stability, efficacy, and clinical potential of diverse bioconjugates to enhance the precision of modern medicine.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115979"},"PeriodicalIF":21.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223133","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

Corrigendum to "Near-infrared fluorescence imaging-guided targeted drug delivery in gastric tumors: From molecular design to clinical translation" [Adv. Drug Deliv. Rev. 235 (2026) 115891]. “近红外荧光成像引导胃肿瘤靶向药物递送：从分子设计到临床翻译”的勘误表[Adv. drug delivery]。Rev. 235(2026) 115891]。

IF 21 1区医学

Advanced drug delivery reviews Pub Date : 2026-09-11 DOI: 10.1016/j.addr.2026.115962

Yuanyuan Ji, Nassuf Mourdi, Kai Bao, Yuanhao Su, Yongke Wu, Zhishen Ge, Hak Soo Choi, Zhidong Wang

引用次数: 0

Bioactive nanomedicines for multidrug-resistant colorectal cancer: Actionable mechanisms, emerging particle classes, and translational barriers. 多药耐药结直肠癌的生物活性纳米药物：可操作的机制，新出现的颗粒类别和翻译障碍。

IF 21 1区医学

Advanced drug delivery reviews Pub Date : 2026-08-15 DOI: 10.1016/j.addr.2026.115957

Milad Rasouli, Fatemeh Babaei, Nadia Fallahhossein, Adeleh Divsalar

{"title":"Bioactive nanomedicines for multidrug-resistant colorectal cancer: Actionable mechanisms, emerging particle classes, and translational barriers.","authors":"Milad Rasouli, Fatemeh Babaei, Nadia Fallahhossein, Adeleh Divsalar","doi":"10.1016/j.addr.2026.115957","DOIUrl":"https://doi.org/10.1016/j.addr.2026.115957","url":null,"abstract":"<p><p>Multidrug resistance (MDR) in colorectal cancer (CRC) arises from interacting tumour-cell, pharmacological and microenvironmental programmes that undermine both drug activity and delivery. Chemotherapy-associated MDR is the principal focus of this review, while resistance to targeted therapy and immunotherapy is considered where it directly affects delivery design or patient selection. Bioactive compounds can modulate several resistance pathways, but their translational value is constrained by poor solubility, instability, rapid metabolism and inadequate exposure at resistant lesions. This review critically examines when nanomedicine can make such mechanistic activity pharmacologically and translationally meaningful. We link resistance biology to delivery functions, evaluate bioactive chemosensitiser candidates against human exposure, compare major nanomedicine design strategies, and assess nano-bio interactions, repeat-dose safety, manufacturing and clinical positioning. Across the evidence, three limitations recur. First, concentrations associated with chemosensitisation for curcumin, resveratrol, epigallocatechin gallate and quercetin generally exceed measured human parent-analyte exposure. Second, many resistance claims rely on parental or poorly characterised models, whereas studies combining defined resistance provenance with functional mechanism and exposure confirmation remain uncommon. Third, human studies demonstrate feasibility, tissue exposure or treatment response, but not mechanism-specific reversal of CRC MDR by a bioactive compound or bioactive nanomedicine. Progress therefore depends less on adding new particle classes than on matching a necessary formulation function to a defined resistance or spatial barrier, quantifying active exposure in the relevant compartment, validating mechanism in appropriate models, and integrating repeat-dose safety, scalable manufacturing and biomarker-guided clinical development.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115957"},"PeriodicalIF":21.0,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757296","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

A toolbox to optimize and scale up microfluidic production of lipid-based nanoparticles. 一个工具箱，以优化和扩大微流体生产的脂基纳米颗粒。

IF 21 1区医学

Advanced drug delivery reviews Pub Date : 2026-08-14 DOI: 10.1016/j.addr.2026.115946

Amr Abostait, Mahmoud Abdelkarim, Arsalan Nikdoost, Pauline Chavrier, Mourad El Hamri, Karine Andrieux, Khair Alhareth, Hagar I Labouta

{"title":"A toolbox to optimize and scale up microfluidic production of lipid-based nanoparticles.","authors":"Amr Abostait, Mahmoud Abdelkarim, Arsalan Nikdoost, Pauline Chavrier, Mourad El Hamri, Karine Andrieux, Khair Alhareth, Hagar I Labouta","doi":"10.1016/j.addr.2026.115946","DOIUrl":"10.1016/j.addr.2026.115946","url":null,"abstract":"<p><p>The use of nanoparticles (NPs) for delivery, particularly for nucleic acid-based therapeutics has become a central determinant of therapeutic efficacy. To ensure safety, potency, and manufacturability across drug development stages, the physicochemical properties of NPs need to be precisely controlled. Microfluidic (MF) synthesis enables great control over the NPs formation process and maintains physicochemical properties across different production scales. MF offers economic advantages for high-throughput screening of large formulation libraries, while delivering superior reproducibility and scalability to meet regulatory requirements. In this review, we map the end-to-end workflow of MF based NPs synthesis and present an integrated \"toolbox\" of technologies to optimize this process for successful drug development. We highlight advances in chip fabrication methods and the critical performance tests required to ensure robust NPs production. We then detail the underlying principles of NPs formation in MF systems and highlight emerging computational and simulation approaches to model and predict NPs assembly. Finally, we examine the incorporation of machine learning tools to establish predictive relationships between process parameters and NPs properties. We anticipate that strategic selection of MF chip design, integrated with chip fabrication technologies, simulation-based approaches, and machine learning tools, can greatly boost experimental optimization, process control, and predictability, ultimately accelerating the clinical translation of NPs-based therapies.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115946"},"PeriodicalIF":21.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757061","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

A strategic guide of techniques for biomedical and tissue engineering applications to measure mechanical properties of soft matter, eye and skin 生物医学和组织工程应用技术的战略指南，以测量软物质，眼睛和皮肤的机械特性

IF 17.6 1区医学

Advanced drug delivery reviews Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.addr.2026.115792

Claudia Muñoz Villaescusa , Diana van der Ven , Miguel A. Quetzeri-Santiago , David Fernandez Rivas

{"title":"A strategic guide of techniques for biomedical and tissue engineering applications to measure mechanical properties of soft matter, eye and skin","authors":"Claudia Muñoz Villaescusa , Diana van der Ven , Miguel A. Quetzeri-Santiago , David Fernandez Rivas","doi":"10.1016/j.addr.2026.115792","DOIUrl":"10.1016/j.addr.2026.115792","url":null,"abstract":"<div><div>A comprehensive understanding of tissue mechanics at the microscale is critical for advancing personalised therapies, controlled drug release, and tissue engineering. Characterising the mechanical properties of complex, soft biological materials—particularly multilayered and anisotropic organs such as the skin and eye—remains a significant challenge due to their variable water content and scale-dependent behaviour. Traditional continuum models and linear material responses often fail to capture the dynamic and nonlinear nature of these tissues under physiologically relevant conditions.</div><div>This review provides a strategic overview of state-of-the-art techniques for probing the mechanical properties of soft biological tissues, with a focus on skin and ocular systems. Our focus on the skin and eye reflects their favourable barrier properties for topical drug delivery. We examine visualisation methods including optical imaging, interferometry, digital image correlation, optical coherence microscopy, and acoustic imaging. In parallel, we assess actuation mechanisms such as indentation, cavitation rheology, and flow elastography, highlighting their suitability for <em>in vivo</em> applications. Each technique is benchmarked against key operational parameters—spatial resolution, acquisition rate, invasiveness, and strain rate—relevant to drug delivery and therapeutic engineering.</div><div>By mapping the landscape of mechanical characterisation tools, this work offers a valuable resource for researchers in biomedical engineering and beyond, including fields such as physics and chemistry, where accurate dynamic analysis of soft complex materials is essential.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"231 ","pages":"Article 115792"},"PeriodicalIF":17.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095684","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

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