Pub Date : 2025-09-01DOI: 10.1016/j.addr.2025.115679
Chunfa Chen , Xiaoyu Xia , Cheng Tian , Zhe Zhang , Jin Jin , Cheng Zhi Huang , Hua Zuo , Chengde Mao
DNA nanotechnology, a cutting-edge field that constructs sophisticated DNA-based nanostructures by harnessing the unparalleled programmability of DNA, has evolved into a powerful tool for applications in therapy, biosensing, logic computation, and more. This review outlines the fundamental strategies for constructing DNA nanostructures, beginning with the design of basic building blocks such as small, symmetric tiles (e.g., DX and TX tiles, point star motifs, T-junctions), and extending to more complex, addressable scaffolds like DNA origami and single-stranded tile (SST) structures. Furthermore, it surveys extended arrays (1D/2D arrays, nanotubes, 3D crystals) formed through motif association, while introducing the computational potential of algorithmic self-assembly and the properties of DNA-based aggregates (hydrogels, liquid–liquid phase separation systems). The design and construction logic of DNA nanostructures, spanning from static to dynamic systems and from microscopic to macroscopic scales, is also elucidated.
{"title":"Design principles for construction of DNA-based nanostructures","authors":"Chunfa Chen , Xiaoyu Xia , Cheng Tian , Zhe Zhang , Jin Jin , Cheng Zhi Huang , Hua Zuo , Chengde Mao","doi":"10.1016/j.addr.2025.115679","DOIUrl":"10.1016/j.addr.2025.115679","url":null,"abstract":"<div><div>DNA nanotechnology, a cutting-edge field that constructs sophisticated DNA-based nanostructures by harnessing the unparalleled programmability of DNA, has evolved into a powerful tool for applications in therapy, biosensing, logic computation, and more. This review outlines the fundamental strategies for constructing DNA nanostructures, beginning with the design of basic building blocks such as small, symmetric tiles (e.g., DX and TX tiles, point star motifs, T-junctions), and extending to more complex, addressable scaffolds like DNA origami and single-stranded tile (SST) structures. Furthermore, it surveys extended arrays (1D/2D arrays, nanotubes, 3D crystals) formed through motif association, while introducing the computational potential of algorithmic self-assembly and the properties of DNA-based aggregates (hydrogels, liquid–liquid phase separation systems). The design and construction logic of DNA nanostructures, spanning from static to dynamic systems and from microscopic to macroscopic scales, is also elucidated.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115679"},"PeriodicalIF":17.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928454","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}
Pub Date : 2025-08-29DOI: 10.1016/j.addr.2025.115678
Sarika A. Jadhav , Ankur J. Raval , Vandana B. Patravale
Drug-eluting stents are the standard therapy for arterial occlusions, particularly in peripheral arterial disease, owing to their efficacy in mitigating in-stent restenosis, maintaining favorable biocompatibility, and improving patient compliance. Their performance can be enhanced through the integration of particulate systems, cytostatic agents, and biodegradable polymers. The complexities associated with chronic disease progression, recurrent in-stent restenosis, the impracticality of long-term animal studies, and the absence of United States Food and Drug Administration-endorsed in vitro drug release protocols for peripheral drug-eluting stents underscore the need for modified strategies and accelerated in vitro release testing as a quality control strategy. In addition to in vitro drug release, other critical evaluation parameters for coated stents include coating uniformity, thickness, drug content, biodegradability, particulate matter, and sterility testing. Ethylene oxide is the most widely used method for the sterilization of drug-eluting stents. Despite their clinical significance, standardized regulatory guidelines and a unified scientific framework for stability testing remain limited. This review provides a comprehensive overview of drug delivery strategies for peripheral drug-eluting stents, coating methodologies, evaluation criteria, in vitro drug release and permeation studies, preclinical animal models, drug release correlations, and stability considerations, along with perspectives on future advancements and opportunities in this field.
{"title":"Drug delivery, development, and technological aspects for peripheral drug eluting stents","authors":"Sarika A. Jadhav , Ankur J. Raval , Vandana B. Patravale","doi":"10.1016/j.addr.2025.115678","DOIUrl":"10.1016/j.addr.2025.115678","url":null,"abstract":"<div><div>Drug-eluting stents are the standard therapy for arterial occlusions, particularly in peripheral arterial disease, owing to their efficacy in mitigating in-stent restenosis, maintaining favorable biocompatibility, and improving patient compliance. Their performance can be enhanced through the integration of particulate systems, cytostatic agents, and biodegradable polymers. The complexities associated with chronic disease progression, recurrent in-stent restenosis, the impracticality of long-term animal studies, and the absence of United States Food and Drug Administration-endorsed <em>in vitro</em> drug release protocols for peripheral drug-eluting stents underscore the need for modified strategies and accelerated <em>in vitro</em> release testing as a quality control strategy. In addition to <em>in vitro</em> drug release, other critical evaluation parameters for coated stents include coating uniformity, thickness, drug content, biodegradability, particulate matter, and sterility testing. Ethylene oxide is the most widely used method for the sterilization of drug-eluting stents. Despite their clinical significance, standardized regulatory guidelines and a unified scientific framework for stability testing remain limited. This review provides a comprehensive overview of drug delivery strategies for peripheral drug-eluting stents, coating methodologies, evaluation criteria, <em>in vitro</em> drug release and permeation studies, preclinical animal models, drug release correlations, and stability considerations, along with perspectives on future advancements and opportunities in this field.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115678"},"PeriodicalIF":17.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915614","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}
Pub Date : 2025-08-29DOI: 10.1016/j.addr.2025.115680
Weihong Yang , Chunyan Ran , Xinran Lian , Zehua Wang , Zhen Du , Tao Bing , Yu Zhang , Weihong Tan
The advent of precision medicine has created an urgent need for advanced drug-targeting strategies and refined drug delivery systems. Aptamers, characterized by their exceptional affinity and specificity, low molecular weight, negligible immunogenicity, remarkable stability, cost-effectiveness, and structural versatility, are emerging as promising candidates in targeted therapeutics, both in preclinical research and clinical applications. This review provides a comprehensive analysis of the latest advancements in aptamer-based therapeutic strategies, encompassing three key application domains: direct therapeutic agents, targeted ligand engineering, and controlled drug release. We will summarize the preclinical applications of aptamers for various disease therapies, including eye disorders, cancers, coagulation, and inflammation. Particular emphasis is placed on emerging clinical-stage aptamer therapeutics undergoing rigorous evaluation for these diseases. Furthermore, we will discuss the potential challenges and unlimited opportunities for the clinical transformation and commercialization of aptamers.
{"title":"Aptamer-based targeted drug delivery and disease therapy in preclinical and clinical applications","authors":"Weihong Yang , Chunyan Ran , Xinran Lian , Zehua Wang , Zhen Du , Tao Bing , Yu Zhang , Weihong Tan","doi":"10.1016/j.addr.2025.115680","DOIUrl":"10.1016/j.addr.2025.115680","url":null,"abstract":"<div><div>The advent of precision medicine has created an urgent need for advanced drug-targeting strategies and refined drug delivery systems. Aptamers, characterized by their exceptional affinity and specificity, low molecular weight, negligible immunogenicity, remarkable stability, cost-effectiveness, and structural versatility, are emerging as promising candidates in targeted therapeutics, both in preclinical research and clinical applications. This review provides a comprehensive analysis of the latest advancements in aptamer-based therapeutic strategies, encompassing three key application domains: direct therapeutic agents, targeted ligand engineering, and controlled drug release. We will summarize the preclinical applications of aptamers for various disease therapies, including eye disorders, cancers, coagulation, and inflammation. Particular emphasis is placed on emerging clinical-stage aptamer therapeutics undergoing rigorous evaluation for these diseases. Furthermore, we will discuss the potential challenges and unlimited opportunities for the clinical transformation and commercialization of aptamers.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115680"},"PeriodicalIF":17.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919189","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}
Pub Date : 2025-08-29DOI: 10.1016/j.addr.2025.115682
Jihoon Won , Seunghye Cho , Kyoung-Ran Kim , Sehoon Kim , Dae-Ro Ahn
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.
{"title":"Engineering in vivo behavior of DNA nanostructures toward organ-targeted drug delivery","authors":"Jihoon Won , Seunghye Cho , Kyoung-Ran Kim , Sehoon Kim , 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":"2025-08-29","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}
Pub Date : 2025-08-25DOI: 10.1016/j.addr.2025.115681
Shujie Li , Yameng Lou , Maartje M.C. Bastings
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 multivalent engineering: 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.
{"title":"Multivalent engineering of bio interfaces with DNA-based nanomaterials","authors":"Shujie Li , Yameng Lou , 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":"2025-08-25","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}
Pub Date : 2025-08-18DOI: 10.1016/j.addr.2025.115676
Tanveer A. Tabish , Craig A. Lygate
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.
{"title":"Nitric oxide releasing graphene for next-generation therapeutics","authors":"Tanveer A. Tabish , 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}
Pub Date : 2025-08-14DOI: 10.1016/j.addr.2025.115675
Yanqing Wang , Da Sun , Victoria Laney , Hong Wang , Li Lily Wang , Zheng-Rong Lu
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.
{"title":"Challenges and opportunities on achieving an adequate delivery efficiency and immunogenicity with peptide-based anticancer vaccines","authors":"Yanqing Wang , Da Sun , Victoria Laney , Hong Wang , Li Lily Wang , 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}
Pub Date : 2025-08-13DOI: 10.1016/j.addr.2025.115672
Jianjun Tao , Yu-Wei Lin , Lingyuxiu Zhong , Yan Zhu , Xinpeng Yao , Michael Aichem , Falk Schreiber , Jinxin Zhao , Jian Li
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.
{"title":"Genome-scale metabolic modelling in antimicrobial pharmacology: Present and future","authors":"Jianjun Tao , Yu-Wei Lin , Lingyuxiu Zhong , Yan Zhu , Xinpeng Yao , Michael Aichem , Falk Schreiber , Jinxin Zhao , 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}
Pub Date : 2025-08-13DOI: 10.1016/j.addr.2025.115674
Zhongyu Cheng , Yanfei Liu , Qiwen Chen , Yifu Tan , Yunqi Man , Zhirou Zhang , Shuqing Du , Zexiang Lv , Qian Wang , Kan Shao , Zhenbao Liu
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.
{"title":"DNA-based nanostructures for cell membrane receptor regulation and disease treatment","authors":"Zhongyu Cheng , Yanfei Liu , Qiwen Chen , Yifu Tan , Yunqi Man , Zhirou Zhang , Shuqing Du , Zexiang Lv , Qian Wang , Kan Shao , 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}
Pub Date : 2025-08-11DOI: 10.1016/j.addr.2025.115673
Haniyeh Abdollahzadeh , Tonya L. Peeples , Mohammad Shahcheraghi
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.
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.
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.
基于DNA的纳米材料由于其独特的性质，包括DNA不同的分子相互作用、可编程性和与生物模块的通用性，在各种应用中显示出巨大的潜力。与此同时，DNA折纸平台在制造药物载体方面显示出了希望。这项技术为生产性能优异的纳米机器铺平了道路。此外，DNA的编码能力及其巨大的并行性帮助我们操纵它进行DNA计算。DNA纳米技术方法具有潜力，特别是在寡核苷酸治疗方面，使癌症的精确医学成为可能。在这篇综述中，我们探讨了DNA纳米技术在这一背景下的潜力，重点关注DNA折纸方法及其生产挑战，并提出了简化的方法，以提高酶工具在类生命人工系统中的可扩展性和效率。然后，我们深入研究了DNA纳米技术在肿瘤靶向递送寡核苷酸药物中的应用。在此之后，我们评估了基于dna的动态纳米器件，这些器件可以通过分子结合、环境刺激和外场操作激活。随后，我们研究了DNA计算在逻辑门、DNA电路、数据存储和机器学习的生产中的意义，以及它在药物递送方法中的作用。通过对DNA机器人的基本操作机制进行系统分类，机械DNA机器人（machine DNA robots, MDNARs）和计算DNA机器人（Computational DNA robots, CDNARs），我们为下一代生物纳米机器人铺平了道路。“这些先进的系统可以将DNA计算与动态DNA机器结合起来，通过智能分子尺度的操作实现精确的癌症治疗。”
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