Advanced drug delivery reviews最新文献

{"title":"Engineering in vivo behavior of DNA nanostructures toward organ-targeted drug delivery","authors":"Jihoon Won ,&nbsp;Seunghye Cho ,&nbsp;Kyoung-Ran Kim ,&nbsp;Sehoon Kim ,&nbsp;Dae-Ro Ahn","doi":"10.1016/j.addr.2025.115682","DOIUrl":"10.1016/j.addr.2025.115682","url":null,"abstract":"<div><div>DNA nanostructures have emerged as programmable and biocompatible platforms for drug delivery, offering precise control over size, shape, and surface properties. Recent advances have demonstrated their potential for organ-targeted delivery by utilizing ligand conjugation, structural engineering, and modulation of protein corona composition. Despite their promise, key challenges remain in predicting organ specificity and ensuring structural stability in vivo. This review provides a comprehensive overview of DNA nanostructures that have demonstrated organ-specific drug delivery, with emphasis on biodistribution profiles, in vivo targeting strategies, and the influence of physicochemical and biological barriers. We also highlight recent insights into corona-assisted targeting and administration route-dependent distribution, outlining strategies to enhance translational potential. Finally, we discuss critical challenges and future directions for clinical application of DNA nanostructures as targeted nanocarriers.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115682"},"PeriodicalIF":17.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915619","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}

{"title":"Bioinspired approaches to encapsulate and deliver bacterial live biotherapeutic products","authors":"Noah Y. Brittain,&nbsp;Joel A. Finbloom","doi":"10.1016/j.addr.2025.115663","DOIUrl":"10.1016/j.addr.2025.115663","url":null,"abstract":"<div><div>Bacteria-based therapies such as live biotherapeutic products (LBPs) allow for the <em>in situ</em> production of bioactive and therapeutic compounds, offering immense potential in the treatment of numerous diseases, including colitis, cancer, and metabolic diseases. While promising, LBPs face numerous delivery barriers that limit their translational potential. Many of these challenges stem from the specific requirements of delivering living bacteria, necessitating delivery systems with distinctive features beyond traditional drug delivery approaches. By taking inspiration from natural biological systems such as bacterial membranes, capsules, and biofilms, researchers can build upon fundamental biological insights combined with advances in materials science, chemical biology, and bioengineering to develop next-generation LBP delivery systems. In this review, we will cover the current progress in bacterial LBPs and major barriers to their delivery. We will then discuss in depth the different bioinspired LBP delivery systems that have been developed and highlight challenges that must be addressed for this nascent field to advance and achieve widespread clinical translation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115663"},"PeriodicalIF":17.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786808","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}

{"title":"Patient-Derived 3D-Bioprinted Models of Pancreatic Cancer: Toward Personalized Therapy and Overcoming Tumor Microenvironment Challenges","authors":"Daniella Vaskovich-Koubi ,&nbsp;Marina Green Buzhor ,&nbsp;Anne Krinsky ,&nbsp;Yair Roth ,&nbsp;Koren Salomon ,&nbsp;Ron Kleiner ,&nbsp;Rina Sevostianov ,&nbsp;Ohad Hasin ,&nbsp;Rami Khoury ,&nbsp;Ronit Satchi-Fainaro","doi":"10.1016/j.addr.2025.115670","DOIUrl":"10.1016/j.addr.2025.115670","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-resistant solid tumors, mainly due to its complex tumor microenvironment (TME). Characterized by dense desmoplastic stroma, immune suppression, and metabolic rewiring, the TME impairs drug delivery and eventually leads to therapeutic failure. Conventional models, such as two-dimensional (2D) cultures and mouse models, fail to recapitulate the cellular and mechanical intricacies of PDAC, limiting their translational relevance.</div><div>Three-dimensional (3D) models have emerged as promising tools to better simulate tumor biology. Among them, 3D-bioprinting techniques enable the precise spatial organization of cancer, stromal, and immune cells within tailored bioinks, supporting physiologically relevant architectures and dynamic microenvironmental interactions. These platforms allow controlled incorporation of extracellular matrix components, tunable stiffness, and perfusable vasculature, improving model fidelity and enabling real-time assessment of drug penetration, immune infiltration, and therapy resistance.</div><div>This review provides a comprehensive overview of current 3D PDAC modeling strategies, emphasizing patient-derived 3D-bioprinted models. We explore the key roles of bioink composition, extracellular matrix (ECM) stiffness, perfusion capacity, and immuno-compatibility in shaping the fidelity and utility of these models. Furthermore, we compare the structural complexity, scalability, drug-screening capabilities, and applicability for personalized medicine of different 3D models. By highlighting advances in vascularization, immune co-culture, and biofabrication technologies, we underscore the emerging value of 3D-bioprinting as a transformative platform for preclinical PDAC research. Ultimately, 3D-bioprinting is an important step forward in bridging the gap between preclinical studies and clinical implementation, as it opens the door to more accurate, personalized, and efficient therapeutic approaches for PDAC.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115670"},"PeriodicalIF":17.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797072","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}

{"title":"Multivalent engineering of bio interfaces with DNA-based nanomaterials","authors":"Shujie Li ,&nbsp;Yameng Lou ,&nbsp;Maartje M.C. Bastings","doi":"10.1016/j.addr.2025.115681","DOIUrl":"10.1016/j.addr.2025.115681","url":null,"abstract":"<div><div>In biology, function rarely depends on a single binding event. Whether it’s cell signaling, immune recognition, or adhesion, most processes rely on a critical density of interactions that occur simultaneously and in close proximity. This multivalency ensures robustness, specificity, and tunability, features that single-molecule targeting approaches often fail to replicate. As a result, there is growing interest in engineering multivalent systems that can mimic or exploit these natural interaction patterns at biointerfaces. DNA-based nanomaterials, with their precise programmability and structural control, have emerged as powerful tools in this space. They enable the spatial organization of ligands at nanometer resolution, not only enhancing binding avidity but also allowing for the design of geometry-dependent and context-sensitive targeting strategies. This capability marks a conceptual shift from traditional multivalent binding toward what we define here as <em>multivalent engineering</em>: the deliberate spatial programming of ligand arrangements to control biological outcomes based on receptor organization, density, and local context. This review discusses the fundamental principles of multivalency at biointerfaces, highlights recent advances in DNA-enabled design strategies, and explores how this emerging framework of multivalent engineering is driving new applications in diagnostics, therapeutics, and synthetic biology. We also outline the major challenges that must be addressed to realize the full potential of these systems in complex in vivo environments.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115681"},"PeriodicalIF":17.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899083","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}

{"title":"The molecular circadian clock: From fundamental mechanisms to therapeutic promise in neurological disorders","authors":"Adam Campbell-Galland ,&nbsp;Akanksha Bafna ,&nbsp;Aarti Jagannath","doi":"10.1016/j.addr.2025.115653","DOIUrl":"10.1016/j.addr.2025.115653","url":null,"abstract":"<div><div>Circadian rhythms are intrinsic biological processes in all forms of life, governed by a molecular clock, organising physiological and behavioural cycles to align with a 24-hour light–dark cycle. The disruption of these rhythms has been linked to a plethora of neurological conditions and impacting cognitive and metabolic functions.</div><div>This review offers a clear overview of the genetic and molecular mechanisms that govern the circadian clock. It focuses on the core clock feedback loops, the pathways involved and how these mechanisms are regulated. We explore how clocks in peripheral tissues are synchronised to the suprachiasmatic nucleus and how this is achieved through neuronal and humoral pathways. Additionally, we discuss how dysregulation in circadian rhythms contribute to neurological conditions and potential therapeutic treatments targeting circadian mechanisms. Understanding the mechanisms of circadian dysregulation provides insight into disease pathology and potential therapies. Interventions targeting circadian mechanisms, such as gene and drug delivery systems, show promise to restore rhythms and mitigate neurological symptoms. This review collates current knowledge on circadian biology and its applications addressing neurological dysfunctions, providing a foundation for potential chronotherapeutic interventions.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115653"},"PeriodicalIF":17.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611397","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}

{"title":"Navigating the complexities of pancreatic ductal adenocarcinoma: A review on therapeutic models and RAS inhibitors","authors":"Sara Barrambana ,&nbsp;Elena Zamorano-Domínguez ,&nbsp;Vasiliki Liaki ,&nbsp;Carmen Guerra","doi":"10.1016/j.addr.2025.115652","DOIUrl":"10.1016/j.addr.2025.115652","url":null,"abstract":"<div><div>Pancreatic cancer is one of the most lethal types of cancer, known for a poor prognosis. Currently, the standard of care for unresectable tumors consists of combinations of cytotoxic chemotherapy. Thus far, targeted therapies against specific oncogenic pathways have not been approved for clinical use. Most cases of pancreatic cancer are sporadic/non-hereditary Pancreatic Ductal Adenocarcinomas (PDACs) and are caused by activating mutations in the <em>KRAS</em> oncogene. For the past four decades, KRAS was considered “undruggable”. However, numerous multi-selective and mutant-specific RAS inhibitors are now under active development. In this review, we present experimental models of PDAC that facilitate studies of response to therapy and drug resistance. We also discuss recent evidence on targeted therapeutic strategies under preclinical and clinical evaluation, with emphasis on the KRAS signaling.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115652"},"PeriodicalIF":15.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586833","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}

{"title":"CRISPR/Cas bioimaging: From whole body biodistribution to single-cell dynamics","authors":"Ekaterina Kolesova ,&nbsp;Sabina Pulone ,&nbsp;Dmitry Kostyushev ,&nbsp;Ennio Tasciotti","doi":"10.1016/j.addr.2025.115619","DOIUrl":"10.1016/j.addr.2025.115619","url":null,"abstract":"<div><div>This review explores the transformative role of CRISPR/Cas systems in optical bioimaging, emphasizing how advancements in nanoparticle (NP) technologies are revolutionizing the visualization of gene-editing processes both <em>in vitro</em> and <em>in vivo</em>. Optical imaging techniques, such as near-infrared (NIR) and fluorescence imaging, have greatly benefited from the integration of nanoformulated contrast agents, improving resolution, sensitivity, and specificity. CRISPR/Cas systems, originally developed just for gene editing, are now being coupled with these imaging modalities to enable real-time monitoring and quantitative measurements of metabolites, vitamins, proteins, nucleic acids and other entities in specific areas of the body, as well as tracking of CRISPR/Cas delivery, editing efficiency, and potential off-target effects. The development of CRISPR/Cas-loaded NPs allows for enhanced imaging and precise monitoring across multiple scales with multiplexed and multicolor imaging in complex settings, including potential <em>in vivo</em> diagnostics. CRISPR/Cas therapeutics as well as diagnostics are hindered by the lack of efficient and targeted delivery tools. Biomimetic NPs have emerged as promising tools for improving biocompatibility, enhancing targeting capabilities, and overcoming biological barriers, facilitating more efficient delivery and bioimaging of CRISPR/Cas systems <em>in vivo</em>. As the design of these NPs and delivery mechanisms improves, alongside advancements in endolysosomal escape, CRISPR/Cas-based bioimaging will continue to advance, offering unprecedented possibilities in precision medicine and theranostic applications.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115619"},"PeriodicalIF":15.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177293","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}

{"title":"Advances in carbon nanomaterials and their polymeric composites in neural tissue engineering","authors":"Baishali Kanjilal ,&nbsp;Prince David Okoro ,&nbsp;Razieh Jaberi ,&nbsp;Ashley Taepakdee ,&nbsp;Nourouddin Sharifi ,&nbsp;Joshua Morgan ,&nbsp;Vijayalakshmi Santhakumar ,&nbsp;Victor G. Rodgers ,&nbsp;Arameh Masoumi ,&nbsp;Iman Noshadi","doi":"10.1016/j.addr.2025.115658","DOIUrl":"10.1016/j.addr.2025.115658","url":null,"abstract":"<div><div>Carbon‐based nanomaterials (CBMs) and their polymeric composites have garnered widespread interest in treating neurotrauma and neurodegenerative diseases, where restoring damaged central and peripheral nervous systems remains a persistent clinical challenge. These materials provide exceptional electrical conductivity, mechanical robustness, and tunable nanoscale architectures conducive to guiding neuronal growth, synaptic connectivity, and targeted biomolecule delivery. In this review, we explore the rationale, recent advances, and translational potential of CBM scaffolds in promoting neuronal survival, neurite outgrowth, and functional maturity across various experimental models. We detail key fabrication strategies, including electrospinning, phase inversion, 3D bioprinting, and pyrolysis that enable precise control over scaffolds’ structural and mechanical properties while facilitating the incorporation of neurotrophic factors, genes, and therapeutic drugs. Emerging <em>in vivo</em> findings suggest that CBM nanocomposites promote regenerative outcomes in peripheral nerve injuries at levels comparable to, or exceeding conventional autografts, underscoring their promise as off‐the‐shelf solutions. Nonetheless, concerns persist regarding large-scale manufacturing, cytotoxicity, and meeting regulatory standards for clinical use. By highlighting cutting-edge innovations and remaining bottlenecks, this review aims to guide future research endeavors in harnessing CBM scaffolds for safe and effective neural tissue repair.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115658"},"PeriodicalIF":17.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684724","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}

{"title":"Carbon dots as multi-modal contrast agents: opportunities and open challenges for in vivo bioimaging","authors":"Elisa Sturabotti ,&nbsp;Beatriz Sierra-Serrano ,&nbsp;Samantha Marcelino Apresto ,&nbsp;Michele Cesco ,&nbsp;Luca Comparini ,&nbsp;Lucia Cardo ,&nbsp;Maurizio Prato","doi":"10.1016/j.addr.2025.115659","DOIUrl":"10.1016/j.addr.2025.115659","url":null,"abstract":"<div><div>Carbon dots (CDs), a class of carbonaceous and fluorescent nanomaterials with ultra-small dimensions (below 10 nm), have become popular nanoparticles in several fields, such as nanomedicine, catalysis, sensing or electronics. Due to their chemical versatility, luminescence, surface functional groups, biocompatibility and water solubility, they have been extensively studied in biomedical field. In this review, we focused on CDs used as nano contrast agents (nCAs) for fluorescence, magnetic resonance or computed tomography imaging in small animal models. We described the advantages of using CDs, highlighting some relevant examples, as well as the current issues that slow down their effective use in biomedicine, such as the rational synthetic design, scant purification and poor characterization. Lastly, we gathered some perspectives to develop carbon dots with more reliable properties and accomplish cutting-edge applications.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115659"},"PeriodicalIF":15.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684929","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}

{"title":"From cell-SELEX to tissue-SELEX for targeted drug delivery and aptamer nanomedicine","authors":"Ka-Ying Wong ,&nbsp;Man-Sau Wong ,&nbsp;Jung Heon Lee ,&nbsp;Juewen Liu","doi":"10.1016/j.addr.2025.115646","DOIUrl":"10.1016/j.addr.2025.115646","url":null,"abstract":"<div><div>Aptamers are nucleic acid-based ligands that can selectively bind to target molecules. Because of their unique target-binding properties, the use of aptamers for targeting cell surface molecules has attracted broad research interest. The field has evolved from selecting aptamers against purified surface proteins to using whole cells (cell-SELEX) as targets. To further advance the field, the concept of tissue-SELEX was later proposed to ensure that selected aptamers possess optimal binding properties in more native <em>in vivo</em> environments. In this article, we review recent progress made for tissue-SELEX, covering methods including tissue slide-based SELEX, morph-X-SELEX, <em>ex vivo</em>-SELEX, and microfluidic tissue-SELEX. The target tissues include cornea, breast, ovary, lung, cardiac and thyroid tissues. For the diseases targeted, cancer is the most extensively studied followed by cardiomyopathies and vascular conditions. The advantages of each method are discussed and potential limitations are also critically reviewed. Applications of tissue- or <em>in vivo</em>-SELEX-derived aptamers in drug delivery include local administration for ocular diseases and systemic administration for lung cancer. Finally, future directions are discussed, emphasizing the need for systematic comparative studies to evaluate cell-SELEX and tissue-SELEX derived aptamers, using antibodies as benchmarks to guide the development of clinically relevant therapeutic applications.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115646"},"PeriodicalIF":15.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565822","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}