Advanced drug delivery reviews最新文献

{"title":"Nitric oxide releasing graphene for next-generation therapeutics","authors":"Tanveer A. Tabish ,&nbsp;Craig A. Lygate","doi":"10.1016/j.addr.2025.115676","DOIUrl":"10.1016/j.addr.2025.115676","url":null,"abstract":"<div><div>Nitric oxide (NO) is a powerful signalling molecule and plays a central role in numerous physiological processes, most notably, in the cardiovascular, immune and central nervous systems. While organic nitrates, exemplified by nitroglycerin, have been used for over a century to deliver therapeutic NO, the search for novel drugs capable of selectively increasing NO bioavailability has continued unabated. Delivery of NO is hindered by its gaseous nature, extreme reactivity, short half-life and potential for systemic toxicity. To address these challenges, controlled NO delivery systems are highly desirable, offering precise release at the site of action over defined periods. Recent advances have focused on nanoparticles for injectable or implantable use, enabling sustained, targeted NO release while degrading safely. Among these, graphene nanostructures have emerged as efficient NO carriers, since they can be specifically designed to deliver NO gas or donor compounds due to their tunable surface chemistry, easy chemical modification and good biocompatibility. In this review, we discuss the latest developments in NO-releasing graphene formulations, alongside key applications in cardiovascular diseases, antimicrobial therapy and cancer treatment.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115676"},"PeriodicalIF":17.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899135","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":"Challenges and opportunities on achieving an adequate delivery efficiency and immunogenicity with peptide-based anticancer vaccines","authors":"Yanqing Wang ,&nbsp;Da Sun ,&nbsp;Victoria Laney ,&nbsp;Hong Wang ,&nbsp;Li Lily Wang ,&nbsp;Zheng-Rong Lu","doi":"10.1016/j.addr.2025.115675","DOIUrl":"10.1016/j.addr.2025.115675","url":null,"abstract":"<div><div>Peptide vaccines are based on small peptide segments that contain antigenic epitopes recognizable by immune cells. Unlike traditional vaccines, they include only specific antigenic epitopes rather than entire pathogens or proteins. They are recognized, internalized, processed, and presented by antigen-presenting cells, such as dendritic cells, and subsequently presented to T cells, triggering an immune response. Peptide-based vaccines, an innovative regimen of cancer immunotherapy, have shown the potential to elicit target-specific anti-tumor immune responses, however their therapeutic efficacy is often diminished by their poor stability, rapid clearance from circulation, low immunogenicity, individual variability, and immune escape. In recent years, significant advancements have been achieved in the mechanism of action, design, and delivery of potent peptide-based cancer vaccines to address their limitations for clinical translation. Long peptide vaccines are more likely to induce antigen cross-presentation than short peptide vaccines. Tumor-specific peptide antigens and tumor-associated antigens have been developed to enhance anti-cancer immunogenicity. Incorporation of various delivery systems, such as lipid nanoparticles, polymers, and viral vectors substantially improve the stability of peptide antigens in circulation. Co-delivery of the peptide antigens and adjuvants further enhances with antigen presentation and T-cell activation, resulting in robust immunogenicity and efficacious cancer immunotherapy. Combination therapy of peptide vaccines and other therapies, including chemotherapy, radiotherapy, immune checkpoint inhibitors, and targeted therapy also enhances therapeutic outcomes. This article provides insights in cancer peptide vaccines, including the mechanism of action of peptide antigens and adjuvants, while discussing their challenges and opportunities, and exploring the use of delivery systems to improve their pharmacokinetics and therapeutic efficacies for cancer immunotherapy.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115675"},"PeriodicalIF":17.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840035","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":"Genome-scale metabolic modelling in antimicrobial pharmacology: Present and future","authors":"Jianjun Tao ,&nbsp;Yu-Wei Lin ,&nbsp;Lingyuxiu Zhong ,&nbsp;Yan Zhu ,&nbsp;Xinpeng Yao ,&nbsp;Michael Aichem ,&nbsp;Falk Schreiber ,&nbsp;Jinxin Zhao ,&nbsp;Jian Li","doi":"10.1016/j.addr.2025.115672","DOIUrl":"10.1016/j.addr.2025.115672","url":null,"abstract":"<div><div>The persistent surge in antimicrobial resistance (AMR) has propelled the search for innovative strategies in antimicrobial use. Genome-scale metabolic modelling (GSMM) has emerged as a transformative tool in this quest, offering a comprehensive understanding of host and microbial metabolism and their interactions with antimicrobial agents. This review emphasises current advancements in the application of GSMM to antimicrobial pharmacology, highlighting its role in deciphering complex microbial and host responses to drug exposure, identifying novel therapeutic targets and optimising therapeutic options. We discuss how GSMM has elucidated mechanisms of drug action, resistance pathways, and off-target effects, providing a systems-level perspective that challenges the traditional “one drug, one target” approach. The integration of GSMM with high-throughput omics technologies and machine learning showcases its potential to refine predictions of drug efficacy, optimise dosing strategies, and minimise toxicity. We also address the challenges and future directions of GSMM, including its expansion to host-pathogen-drug interactions and personalised medicine. Ultimately, GSMM stands as a critical approach in modern antimicrobial research, with the potential to revolutionise the development of effective treatments against MDR pathogens.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115672"},"PeriodicalIF":17.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825759","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":"DNA-based nanostructures for cell membrane receptor regulation and disease treatment","authors":"Zhongyu Cheng ,&nbsp;Yanfei Liu ,&nbsp;Qiwen Chen ,&nbsp;Yifu Tan ,&nbsp;Yunqi Man ,&nbsp;Zhirou Zhang ,&nbsp;Shuqing Du ,&nbsp;Zexiang Lv ,&nbsp;Qian Wang ,&nbsp;Kan Shao ,&nbsp;Zhenbao Liu","doi":"10.1016/j.addr.2025.115674","DOIUrl":"10.1016/j.addr.2025.115674","url":null,"abstract":"<div><div>The aberrant expression and dysfunction of cell membrane receptors are closely associated with the onset and progression of various major diseases, such as cancer, neurodegenerative disorders, and inflammation. However, conventional membrane protein regulation strategies, such as small-molecule inhibitors or antibody-based therapies, face several challenges, including target dependency, limited degradation scope, and the development of drug resistance. In recent years, DNA nanostructure has emerged as an innovative solution for the precise modulation of membrane receptors, owing to its high programmability, precise spatial control, and dynamic responsiveness. This review provides a comprehensive overview of the design strategies and recent progress in the application of DNA nanostructures for membrane protein regulation, with a particular emphasis on their pivotal roles in spatial blockade, spatial reorganization, and targeted degradation of membrane receptors. By rationally designing DNA origami, aptamer-based nanoarrays, and dynamic responsive devices, researchers have achieved precise control over receptor dimerization, oligomerization, and membrane compartmentalization, thereby modulating downstream signaling pathways. In addition, DNA nano-degradation platforms based on proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimeras (LYTACs), and the autophagy-lysosome pathway have significantly enhanced the efficiency of membrane protein degradation while demonstrating excellent tumor selectivity. DNA nanostructures have been successfully applied in cancer immunotherapy, interventions for neurodegenerative diseases, and the regulation of metabolic disorders, offering new strategies for targeting previously “undruggable” proteins. This review highlights recent breakthroughs in the field and outlines future directions and clinical translation potential of DNA nanostructures for membrane protein regulation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115674"},"PeriodicalIF":17.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825465","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":"DNA nanotechnology in oligonucleotide drug delivery systems: Prospects for Bio-nanorobots in cancer treatment","authors":"Haniyeh Abdollahzadeh ,&nbsp;Tonya L. Peeples ,&nbsp;Mohammad Shahcheraghi","doi":"10.1016/j.addr.2025.115673","DOIUrl":"10.1016/j.addr.2025.115673","url":null,"abstract":"<div><div>DNA-based nanomaterials have demonstrated significant potential in various applications due to their unique properties, including DNA’s diverse molecular interactions, programmability, and versatility with biological modules. Meanwhile, the DNA origami platforms have shown promise in the creation of drug carriers. This technique has paved the way for the production of nanomachines with outstanding performance. Moreover, DNA’s encoding capability and its massive parallelism help us to manipulate it for DNA computation. The DNA nanotechnology method holds potential, particularly for oligonucleotide therapeutics that enable precision medicine for cancers.</div><div>In this review, we explore the potential of DNA nanotechnology in this context, focusing on the DNA origami method and its production challenges, and proposing streamlined methods to enhance scalability and efficiency by enzymatic tools in life-like artificial systems. We then delve into studies demonstrating the application of DNA nanotechnology in delivering oligonucleotide drugs for tumor targeting. Following this, we assess DNA-based dynamic nanodevices that can be activated through molecular binding, environmental stimuli, and external field manipulation. Subsequently, we investigate the significance of DNA computation in the production of logic gates, DNA circuits, data storage, and machine learning, along with its role in drug delivery approaches.</div><div>By systematically classifying DNA robots according to their fundamental operating mechanisms, Machinery DNA Robots (MDNARs) and Computational DNA Robots (CDNARs), we pave the way for next-generation ’Bio-nanorobots.’ These advanced systems can integrate DNA computation with dynamic DNA machinery to enable precision cancer therapeutics through intelligent molecular-scale operations.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115673"},"PeriodicalIF":17.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819097","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":"Classic versus innovative strategies for immuno-therapy in pancreatic cancer","authors":"Maria Giovanna Formelli ,&nbsp;Andrea Palloni ,&nbsp;Simona Tavolari ,&nbsp;Chiara Deiana ,&nbsp;Elisa Andrini ,&nbsp;Mariacristina Di Marco ,&nbsp;Davide Campana ,&nbsp;Giuseppe Lamberti ,&nbsp;Giovanni Brandi","doi":"10.1016/j.addr.2025.115671","DOIUrl":"10.1016/j.addr.2025.115671","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Immunotherapy with immune checkpoint inhibitors (ICIs), either as monotherapy, in combination with other ICIs, or alongside chemotherapy, has significantly improved outcomes in several solid tumors. However, its efficacy in PDAC remains limited due to multiple resistance mechanisms.</div><div>Key determinants of immunotherapy resistance in PDAC include physical barriers that hinder immune cells infiltration, such as aberrant vasculature, cancer-associated fibroblasts (CAFs), and excessive hyaluronic acid deposition in the tumor microenvironment (TME). Additionally, PDAC is characterized by an immunosuppressive TME enriched with regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and by low immunogenicity of tumor cells due to KRAS mutations, MYC overexpression, and a low tumor mutational burden, further impairing antitumor immunity.</div><div>This review discusses advanced drug delivery systems to overcome determinants of immunotherapy resistance and to improve outcomes, explores emerging immunotherapy strategies, including adoptive cell therapies, cancer vaccines, and the potential role of microbiota as modulator of TME through fecal microbiota transplantation or intratumoral bacterial inoculation. Given the ambivalent role of microbiota in PDAC, the need for a clear definition of favorable strains and their selection is highlighted. Emerging approaches involving engineered bacteria and artificial intelligence applications are also explored.</div><div>Finally, we propose a hypothetical conceptual framework for an innovative multimodal immunotherapy approach to overcome resistance and improve clinical outcomes in PDAC.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"225 ","pages":"Article 115671"},"PeriodicalIF":17.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797075","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":"2025-08-07","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":"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":"2025-08-06","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":"Predicting population dynamics of antimicrobial resistance using mechanistic modeling and machine learning","authors":"Zhengqing Zhou, Irida Shyti, Jaemin Kim, Lingchong You","doi":"10.1016/j.addr.2025.115661","DOIUrl":"https://doi.org/10.1016/j.addr.2025.115661","url":null,"abstract":"Antimicrobial resistance (AMR) infections have become a global public health burden. The pipeline for new antibiotic discovery is draining due to the rapid emergence of resistance to new antibiotics, the limited economic return, and regulatory hurdles. Current strategies to combat the AMR crisis include improving clinical practices under antibiotic stewardship and repurposing FDA-approved drugs. Quantitative modeling of the population dynamics of AMR can inform these strategies by identifying key mechanisms and consequences of resistance development and predicting resistance persistence, with the potential of guiding treatment design. Here we review the current progress of using mechanistic and machine learning (ML) models to understand and predict the population dynamics of AMR in microbial communities. We highlight the current challenges in mechanistic model construction, explore how ML can overcome these limitations, and discuss the translational potential of the computational models.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"31 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786809","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":"Applications of DNA-based nanostructures in immunotherapy","authors":"Dandan Li ,&nbsp;Huarui Liu ,&nbsp;Xintong Li ,&nbsp;Changping Yang ,&nbsp;Hanyin Zhu ,&nbsp;Hong Wang ,&nbsp;Jianbing Liu ,&nbsp;Baoquan Ding","doi":"10.1016/j.addr.2025.115660","DOIUrl":"10.1016/j.addr.2025.115660","url":null,"abstract":"<div><div>DNA, as a carrier of genetic information, has further been efficiently utilized as a foundational element in creating diverse nanostructures of different shapes and sizes through precise base pairing. With spatial addressability, structural programmability, and remarkable biocompatibility, self-assembled DNA-based nanostructures have been broadly applied in various biomedical research areas, such as bio-imaging, disease diagnosis, and drug delivery. Of particular note, immunotherapy, known for its outstanding therapeutic efficacy, has garnered much attention. In this review, we highlight the recent applications of DNA-based nanostructures (including DNA junction, DNA polyhedron, DNA origami, RCA-based DNA structure, DNA hydrogel, and spherical nucleic acid) in immunotherapy (based on the delivery of CpG adjuvant, tumor antigen, PD1 inhibitor, mRNA vaccine, virus antigen, or direct regulating immune cells). Furthermore, the challenges and future prospects of DNA-based nanostructures for <em>in vivo</em> immunotherapy are discussed.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115660"},"PeriodicalIF":17.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737742","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}