Pub Date : 2025-09-25DOI: 10.1016/j.addr.2025.115695
Stefana Duca , Sara Jamshidi Parvar , Luke Kumeta , Tracey D. Bradshaw , Weng C. Chan , Felicity de Cogan , Karolina Dziemidowicz , Pavel Gershkovich , Maria Marlow , Christopher J. Morris , David Shorthouse , Andrew L. Lewis
Diffuse midline gliomas (DMGs) are a highly aggressive and inoperable type of paediatric brain tumours, with a median survival of less than one year. Therapeutic progress has been hindered by the tumour’s anatomical location, its extensive molecular heterogeneity, and the restrictive nature of the blood brain barrier (BBB) in drug delivery. This article explores the current therapeutic landscape of DMG and evaluates emerging drug delivery strategies, including oral, intravenous and intrathecal administration, convection-enhanced delivery (CED), and intranasal approaches, designed to improve drug access to the brain. Advancements in these methods, combined with targeted therapies tailored to the tumour’s unique molecular features, represent a critical pathway towards improving clinical outcomes for DMG patients.
{"title":"Drug delivery strategies for paediatric diffuse midline gliomas","authors":"Stefana Duca , Sara Jamshidi Parvar , Luke Kumeta , Tracey D. Bradshaw , Weng C. Chan , Felicity de Cogan , Karolina Dziemidowicz , Pavel Gershkovich , Maria Marlow , Christopher J. Morris , David Shorthouse , Andrew L. Lewis","doi":"10.1016/j.addr.2025.115695","DOIUrl":"10.1016/j.addr.2025.115695","url":null,"abstract":"<div><div>Diffuse midline gliomas (DMGs) are a highly aggressive and inoperable type of paediatric brain tumours, with a median survival of less than one year. Therapeutic progress has been hindered by the tumour’s anatomical location, its extensive molecular heterogeneity, and the restrictive nature of the blood brain barrier (BBB) in drug delivery. This article explores the current therapeutic landscape of DMG and evaluates emerging drug delivery strategies, including oral, intravenous and intrathecal administration, convection-enhanced delivery (CED), and intranasal approaches, designed to improve drug access to the brain. Advancements in these methods, combined with targeted therapies tailored to the tumour’s unique molecular features, represent a critical pathway towards improving clinical outcomes for DMG patients.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115695"},"PeriodicalIF":17.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134377","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 : 2025-09-25DOI: 10.1016/j.addr.2025.115698
Marta Łaszcz , Magdalena Urbanowicz , Ewelina Baran , Piotr Kulinowski
The potential advantages of pharmaceutical additive manufacturing (AM) are thoroughly described in the literature. Challenges related to pharmaceutical AM are less discussed. Selective laser sintering (SLS) is one of the AM methods possible for pharmaceutical applications. The article addresses aspects of SLS that are not typically explored in pharmaceutical studies. The literature research was conducted in parallel for both non-pharmaceutical (technical) and pharmaceutical SLS. As a result, in-depth studies on the temperature-dependent properties (rheological and optical) and thermal properties of powders for general technical printing are presented, along with the characterization of the laser sintering process. Special attention is given to the development of the “processing window” and “energy density” terms, as they continue to evolve. An application of a wide range of thermal analysis techniques is presented, including fast differential calorimetry, hot-stage microscopy, thermovision, and dielectric thermal analysis. Next, the complexity, regarding crystalline/semicrystalline/amorphous substances combination and their melt miscibility for pharmaceutical powders is marked. Pharmaceutical SLS studies are also analyzed, with emphasis on thermal aspects. Generally, pharmaceutical studies lack meaningful temperature-dependent and thermal analysis. The only significant exception is studies on drug substance amorphization during the SLS process. The main message is that pharmaceutical SLS should benefit from the methods and ideas developed for technical SLS. In particular, the research directions should include: (1) conscious powder design regarding the specificity of SLS manufacturing method, which completely different from powder compression (API - excipients matching), (2) extending the set of research methods, (3) consolidation process elucidation, (4) powder reusing or powder reusing avoiding, (5) searching for potential new carriers/excipients dedicated to pharmaceutical SLS process.
{"title":"Toward pharmaceutical selective laser sintering 3D printing - a thermal and temperature-dependent analysis perspective","authors":"Marta Łaszcz , Magdalena Urbanowicz , Ewelina Baran , Piotr Kulinowski","doi":"10.1016/j.addr.2025.115698","DOIUrl":"10.1016/j.addr.2025.115698","url":null,"abstract":"<div><div>The potential advantages of pharmaceutical additive manufacturing (AM) are thoroughly described in the literature. Challenges related to pharmaceutical AM are less discussed. Selective laser sintering (SLS) is one of the AM methods possible for pharmaceutical applications. The article addresses aspects of SLS that are not typically explored in pharmaceutical studies. The literature research was conducted in parallel for both non-pharmaceutical (technical) and pharmaceutical SLS. As a result, in-depth studies on the temperature-dependent properties (rheological and optical) and thermal properties of powders for general technical printing are presented, along with the characterization of the laser sintering process. Special attention is given to the development of the “processing window” and “energy density” terms, as they continue to evolve. An application of a wide range of thermal analysis techniques is presented, including fast differential calorimetry, hot-stage microscopy, thermovision, and dielectric thermal analysis. Next, the complexity, regarding crystalline/semicrystalline/amorphous substances combination and their melt miscibility for pharmaceutical powders is marked. Pharmaceutical SLS studies are also analyzed, with emphasis on thermal aspects. Generally, pharmaceutical studies lack meaningful temperature-dependent and thermal analysis. The only significant exception is studies on drug substance amorphization during the SLS process. The main message is that pharmaceutical SLS should benefit from the methods and ideas developed for technical SLS. In particular, the research directions should include: (1) conscious powder design regarding the specificity of SLS manufacturing method, which completely different from powder compression (API - excipients matching), (2) extending the set of research methods, (3) consolidation process elucidation, (4) powder reusing or powder reusing avoiding, (5) searching for potential new carriers/excipients dedicated to pharmaceutical SLS process.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"227 ","pages":"Article 115698"},"PeriodicalIF":17.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140546","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 : 2025-09-25DOI: 10.1016/j.addr.2025.115692
Yingying Li , Tatiana N. Zamay , Natalia A. Luzan , Evgeny A. Pryakhin , Elena V. Styazhkina , Liubov A. Osminkina , Olga S. Kolovskaya , Maya A. Dymova , Elena V. Kuligina , Vladimir A. Richter , Alena G. Bkhattachariia , Dmitry A. Bydanov , Alexander V. Galantsev , Ivan A. Vostrov , Zhenbao Liu , Galina S. Zamay , Anna S. Kichkailo , Xue-Qiang Wang
Cancer treatment has transitioned from traditional chemotherapy to the molecular medicine era, emphasizing personalized therapy at the molecular level. Aptamers, also known as ’chemical antibodies’, play a pivotal role in advancing molecular medicine. Utilizing the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique, these aptamers exhibit exceptional affinity for a wide range of targets, ranging from picomolar to nanomolar levels. Their exceptional characteristics, including ease of preparation, small size, low immunogenicity, remarkable chemical stability, and convenient modification, make them highly versatile for precise cancer therapy. Notably, aptamers have been successfully combined with therapeutic agents, such as small interfering RNAs (siRNAs), microRNAs (miRNAs), and small molecule toxins for diverse research purposes. This review article will primarily focus on recent progress in aptamer-based targeted therapy for cancer, offering readers a comprehensive insight into the latest developments in aptamer-based cancer treatment.
{"title":"Aptamers as a new frontier in targeted cancer therapy","authors":"Yingying Li , Tatiana N. Zamay , Natalia A. Luzan , Evgeny A. Pryakhin , Elena V. Styazhkina , Liubov A. Osminkina , Olga S. Kolovskaya , Maya A. Dymova , Elena V. Kuligina , Vladimir A. Richter , Alena G. Bkhattachariia , Dmitry A. Bydanov , Alexander V. Galantsev , Ivan A. Vostrov , Zhenbao Liu , Galina S. Zamay , Anna S. Kichkailo , Xue-Qiang Wang","doi":"10.1016/j.addr.2025.115692","DOIUrl":"10.1016/j.addr.2025.115692","url":null,"abstract":"<div><div>Cancer treatment has transitioned from traditional chemotherapy to the molecular medicine era, emphasizing personalized therapy at the molecular level. Aptamers, also known as ’chemical antibodies’, play a pivotal role in advancing molecular medicine. Utilizing the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique, these aptamers exhibit exceptional affinity for a wide range of targets, ranging from picomolar to nanomolar levels. Their exceptional characteristics, including ease of preparation, small size, low immunogenicity, remarkable chemical stability, and convenient modification, make them highly versatile for precise cancer therapy. Notably, aptamers have been successfully combined with therapeutic agents, such as small interfering RNAs (siRNAs), microRNAs (miRNAs), and small molecule toxins for diverse research purposes. This review article will primarily focus on recent progress in aptamer-based targeted therapy for cancer, offering readers a comprehensive insight into the latest developments in aptamer-based cancer treatment.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115692"},"PeriodicalIF":17.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134376","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 : 2025-09-12DOI: 10.1016/j.addr.2025.115696
Paul Cressey, Shazwan Bin Abd Shukor, Maya Thanou
Sonodynamic therapy (SDT) is an emerging therapeutic modality against hard-to-treat tumours. It involves the use of ultrasound (US) to excite sono-sensitive moieties to produce reactive oxygen species (ROS), which induce tumour cell death. SDT employs the synergetic application of enabling chemicals named sonosensitizers and low-intensity ultrasound. Compared with photodynamic therapy, SDT has the significant advantages of deeper tissue penetration, higher accuracy, and potentially fewer adverse effects if well-designed. There are multiple suggested mechanisms for activating sonosensitizers for SDT, including sonoluminescence, pyrolysis and direct mechanical activation. However, a highly reported mechanism of action and the focus for this review is sonoluminescence (SL). SL is defined as the light generated by catastrophic implosions of oscillating bubbles in a liquid under exposure to ultrasound (US). SL has been shown to interact with sensitising molecules similar to photodynamic therapy to generate ROS. This mechanism involves delocalisation of the excited electron and subsequent transfer from excited sonosensitizers to nearby oxygen molecules (H2O and O2) in the surrounding tissues to produce ROS such as superoxides, peroxides, singlet oxygen and hydroxyl radicals. In SDT, both SL and sonosensitizers play a role in generating enough ROS to initiate the observed anticancer effects. These effects have been investigated in in vitro, in vivo and recently applied in clinical settings. There are several questions pertaining to the efficiency and safety of SDT and sonosensitizers for anticancer treatment, especially in hard-to-treat tumours, which are discussed here. Although the application of SDT has rapidly reached the clinical phase, fundamental studies are still needed to address and understand the complex mechanisms involved in the anticancer effect of SDT.
{"title":"Sonodynamic therapy: transforming sound into light for hard-to-treat tumours","authors":"Paul Cressey, Shazwan Bin Abd Shukor, Maya Thanou","doi":"10.1016/j.addr.2025.115696","DOIUrl":"10.1016/j.addr.2025.115696","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT) is an emerging therapeutic modality against hard-to-treat tumours. It involves the use of ultrasound (US) to excite sono-sensitive moieties to produce reactive oxygen species (ROS), which induce tumour cell death. SDT employs the synergetic application of enabling chemicals named sonosensitizers and low-intensity ultrasound. Compared with photodynamic therapy, SDT has the significant advantages of deeper tissue penetration, higher accuracy, and potentially fewer adverse effects if well-designed. There are multiple suggested mechanisms for activating sonosensitizers for SDT, including sonoluminescence, pyrolysis and direct mechanical activation. However, a highly reported mechanism of action and the focus for this review is sonoluminescence (SL). SL is defined as the light generated by catastrophic implosions of oscillating bubbles in a liquid under exposure to ultrasound (US). SL has been shown to interact with sensitising molecules similar to photodynamic therapy to generate ROS. This mechanism involves delocalisation of the excited electron and subsequent transfer from excited sonosensitizers to nearby oxygen molecules (H<sub>2</sub>O and O<sub>2</sub>) in the surrounding tissues to produce ROS such as superoxides, peroxides, singlet oxygen and hydroxyl radicals. In SDT, both SL and sonosensitizers play a role in generating enough ROS to initiate the observed anticancer effects. These effects have been investigated in <em>in vitro</em>, <em>in vivo</em> and recently applied in clinical settings. There are several questions pertaining to the efficiency and safety of SDT and sonosensitizers for anticancer treatment, especially in hard-to-treat tumours, which are discussed here. Although the application of SDT has rapidly reached the clinical phase, fundamental studies are still needed to address and understand the complex mechanisms involved in the anticancer effect of SDT.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115696"},"PeriodicalIF":17.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043386","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 : 2025-09-12DOI: 10.1016/j.addr.2025.115697
Dharini Srinivasan , Johann Gout , Alexander Kleger , Elodie Roger
In the past decade, single-cell-resolved approaches have uncovered the extensive heterogeneity of pancreatic ductal adenocarcinoma (PDAC), reshaping our understanding of this complex solid tumor. PDAC entities exhibit both intra- and inter-tumor heterogeneity at the tumor and stromal levels, translating into distinct ecosystems and functions, ultimately impacting disease progression and treatment response. Increasing evidence highlights how specific genetic alterations drive unique tumor microenvironment landscapes, affecting fibroblast programming, immune cell contexture and extracellular matrix remodeling. In this review, we emphasize the importance of deciphering and stratifying heterogeneous tumor-stroma networks and provide an overview on the intricate crosstalk linking tumor identity and stromal phenotype. We further discuss the concept of multicellular subtyping and the role of spatial organization in shaping patient outcomes to refine prognostic and therapeutic stratification. Lastly, we explore existing and potential therapeutic strategies aimed at targeting both tumor-intrinsic and stromal-extrinsic vulnerabilities, offering insights into approaches that could enhance the efficacy of tailored treatment schemes. By integrating these perspectives, we aim to provide a comprehensive framework for advancing precision medicine in PDAC.
{"title":"Tumor microenvironment subtyping in pancreatic ductal adenocarcinoma: New avenues for personalized therapeutic strategies","authors":"Dharini Srinivasan , Johann Gout , Alexander Kleger , Elodie Roger","doi":"10.1016/j.addr.2025.115697","DOIUrl":"10.1016/j.addr.2025.115697","url":null,"abstract":"<div><div>In the past decade, single-cell-resolved approaches have uncovered the extensive heterogeneity of pancreatic ductal adenocarcinoma (PDAC), reshaping our understanding of this complex solid tumor. PDAC entities exhibit both intra- and inter-tumor heterogeneity at the tumor and stromal levels, translating into distinct ecosystems and functions, ultimately impacting disease progression and treatment response. Increasing evidence highlights how specific genetic alterations drive unique tumor microenvironment landscapes, affecting fibroblast programming, immune cell contexture and extracellular matrix remodeling. In this review, we emphasize the importance of deciphering and stratifying heterogeneous tumor-stroma networks and provide an overview on the intricate crosstalk linking tumor identity and stromal phenotype. We further discuss the concept of multicellular subtyping and the role of spatial organization in shaping patient outcomes to refine prognostic and therapeutic stratification. Lastly, we explore existing and potential therapeutic strategies aimed at targeting both tumor-intrinsic and stromal-extrinsic vulnerabilities, offering insights into approaches that could enhance the efficacy of tailored treatment schemes. By integrating these perspectives, we aim to provide a comprehensive framework for advancing precision medicine in PDAC.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115697"},"PeriodicalIF":17.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043168","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 : 2025-09-07DOI: 10.1016/j.addr.2025.115685
Agbor Otu Egbe Vydaline , Sergei Rozhkov , German Sosa , Prabodhika Mallikaratchy
Targeted drug delivery significantly enhances therapeutic efficacy across various diseases, particularly in cancer treatments, where conventional approaches such as chemotherapy and radiotherapy often cause severe side effects. In this context, nucleic acid aptamers—short, single-stranded DNA or RNA oligonucleotides capable of binding specific targets with high affinity—have emerged as promising tools for precision drug delivery and therapy. Aptamers can be selected against whole, living cells using SELEX and chemically modified for diverse applications. Their chemical versatility and specific binding capabilities allow aptamers to be engineered into aptamer-drug conjugates, nanoparticles, DNA origami structures, and bi-/multivalent or bispecific constructs. These platforms enable selective recognition of unique molecular signatures on cells or small molecules, facilitating highly targeted drug delivery and controlled release at the disease site. Such precision reduces systemic toxicity and enhances therapeutic outcomes. Compared to antibodies, aptamers offer several advantages, including faster tissue penetration, lower immunogenicity, greater chemical stability, and improved bioavailability in vivo. This review highlights recent advances in aptamer modification strategies—both covalent and non-covalent—for conjugation with chemotherapeutic agents, gold nanoparticles (GNPs), and photosensitizers. We further assess their potential as drug delivery vehicles and therapeutic agents and discuss how these innovations are driving progress in precision medicine.
{"title":"Aptamers as target-specific recognition elements in drug delivery","authors":"Agbor Otu Egbe Vydaline , Sergei Rozhkov , German Sosa , Prabodhika Mallikaratchy","doi":"10.1016/j.addr.2025.115685","DOIUrl":"10.1016/j.addr.2025.115685","url":null,"abstract":"<div><div>Targeted drug delivery significantly enhances therapeutic efficacy across various diseases, particularly in cancer treatments, where conventional approaches such as chemotherapy and radiotherapy often cause severe side effects. In this context, nucleic acid aptamers—short, single-stranded DNA or RNA oligonucleotides capable of binding specific targets with high affinity—have emerged as promising tools for precision drug delivery and therapy. Aptamers can be selected against whole, living cells using SELEX and chemically modified for diverse applications. Their chemical versatility and specific binding capabilities allow aptamers to be engineered into aptamer-drug conjugates, nanoparticles, DNA origami structures, and bi-/multivalent or bispecific constructs. These platforms enable selective recognition of unique molecular signatures on cells or small molecules, facilitating highly targeted drug delivery and controlled release at the disease site. Such precision reduces systemic toxicity and enhances therapeutic outcomes. Compared to antibodies, aptamers offer several advantages, including faster tissue penetration, lower immunogenicity, greater chemical stability, and improved bioavailability in vivo. This review highlights recent advances in aptamer modification strategies—both covalent and non-covalent—for conjugation with chemotherapeutic agents, gold nanoparticles (GNPs), and photosensitizers. We further assess their potential as drug delivery vehicles and therapeutic agents and discuss how these innovations are driving progress in precision medicine.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115685"},"PeriodicalIF":17.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007231","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 : 2025-09-05DOI: 10.1016/j.addr.2025.115677
Karen M. Mancera Azamar , Samanvitha Deepthi Sudi , Zahra Mohammadalizadeh , Carleigh Coffin , Ivana K. Parker , Ana Maria Porras
The human microbiome plays a critical role in health and disease. Disruptions in microbiota composition or function have been implicated not only as markers but also as drivers of diverse pathologies, creating opportunities for targeted microbiome interventions. Advancing these therapies requires experimental models that can unravel the complex, bidirectional interactions between human tissue and microbial communities. This scoping review examines emerging engineering approaches to design in vitro platforms that successfully integrate host and microbial components to model these interactions. Compared to traditional in vitro and in vivo approaches, these advanced microphysiological systems offer greater experimental control, human-specific biology, and reduced cost and ethical concerns. Here, we identify key challenges in the creation of these in vitro models and innovative solutions to address them by leveraging microfluidics, biomaterials, and organoid technologies, among others. These strategies have enabled the development of co-culture systems that replicate critical features of host-microbiome interfaces, including mucosal barriers, oxygen and pH gradients, mechanical stimuli, and host cell diversity. We also describe how these physiologically relevant models are uncovering new insights into epithelial-microbiota crosstalk, immune modulation by commensal microbes, and systemic effects of microbiota and their metabolites across multiple body sites. We conclude by discussing opportunities to expand these systems in scale, complexity, and clinical relevance. As these models continue to evolve, they hold the potential to transform our ability to mechanistically probe microbiome interactions, personalize therapeutic strategies, and accelerate the translation of microbiome science into clinical practice.
{"title":"Innovative engineering approaches to model host-microbiome interactions in vitro","authors":"Karen M. Mancera Azamar , Samanvitha Deepthi Sudi , Zahra Mohammadalizadeh , Carleigh Coffin , Ivana K. Parker , Ana Maria Porras","doi":"10.1016/j.addr.2025.115677","DOIUrl":"10.1016/j.addr.2025.115677","url":null,"abstract":"<div><div>The human microbiome plays a critical role in health and disease. Disruptions in microbiota composition or function have been implicated not only as markers but also as drivers of diverse pathologies, creating opportunities for targeted microbiome interventions. Advancing these therapies requires experimental models that can unravel the complex, bidirectional interactions between human tissue and microbial communities. This scoping review examines emerging engineering approaches to design <em>in vitro</em> platforms that successfully integrate host and microbial components to model these interactions. Compared to traditional <em>in vitro</em> and <em>in vivo</em> approaches, these advanced microphysiological systems offer greater experimental control, human-specific biology, and reduced cost and ethical concerns. Here, we identify key challenges in the creation of these <em>in vitro</em> models and innovative solutions to address them by leveraging microfluidics, biomaterials, and organoid technologies, among others. These strategies have enabled the development of co-culture systems that replicate critical features of host-microbiome interfaces, including mucosal barriers, oxygen and pH gradients, mechanical stimuli, and host cell diversity. We also describe how these physiologically relevant models are uncovering new insights into epithelial-microbiota crosstalk, immune modulation by commensal microbes, and systemic effects of microbiota and their metabolites across multiple body sites. We conclude by discussing opportunities to expand these systems in scale, complexity, and clinical relevance. As these models continue to evolve, they hold the potential to transform our ability to mechanistically probe microbiome interactions, personalize therapeutic strategies, and accelerate the translation of microbiome science into clinical practice.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115677"},"PeriodicalIF":17.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995435","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 : 2025-09-05DOI: 10.1016/j.addr.2025.115684
Xuehui Rui , Yiyang Jia , Ruochen Qiao , Xiaoting Peng , Yuchen Wang , Tao Li , Chuan Zhao , Jinhui Wu
Oxygen plays a critical regulatory role in tissue repair and regeneration. However, in the microenvironment of tissues with vascular damage, hypoxia is commonly present. This not only suppresses cell proliferation and differentiation but also delays angiogenesis and extracellular matrix reconstruction, ultimately hindering the tissue regeneration process. Therefore, developing oxygen delivery strategies that can effectively enhance local oxygen levels has become one of the key approaches to promoting tissue regeneration. Traditional oxygen delivery strategies for tissue regeneration face several challenges, including inadequate sustained oxygen supply, poor targeting ability, and limited biocompatibility. To address these limitations, researchers have developed a variety of “intelligent oxygen delivery systems.” These systems can dynamically regulate oxygen release and achieve tissue-specific targeted delivery by responding to environmental or external stimuli, thereby significantly improving the precision and efficacy of oxygen therapy. This review systematically summarizes the biological functions of oxygen in tissue regeneration, with a particular focus on intelligent strategies for oxygen generation and supply developed in recent years. In addition, this review discusses the oxygen generation mechanisms, release kinetics, biocompatibility, application potential, and limitations of various oxygen delivery strategies. Finally, the review emphasizes that future designs of oxygen delivery systems should place greater emphasis on intelligent regulation, aiming to facilitate their clinical translation in tissue regeneration-related diseases such as chronic wounds, bone repair, and myocardial infarction.
{"title":"Recent advances in intelligent oxygen delivery systems for tissue regeneration","authors":"Xuehui Rui , Yiyang Jia , Ruochen Qiao , Xiaoting Peng , Yuchen Wang , Tao Li , Chuan Zhao , Jinhui Wu","doi":"10.1016/j.addr.2025.115684","DOIUrl":"10.1016/j.addr.2025.115684","url":null,"abstract":"<div><div>Oxygen plays a critical regulatory role in tissue repair and regeneration. However, in the microenvironment of tissues with vascular damage, hypoxia is commonly present. This not only suppresses cell proliferation and differentiation but also delays angiogenesis and extracellular matrix reconstruction, ultimately hindering the tissue regeneration process. Therefore, developing oxygen delivery strategies that can effectively enhance local oxygen levels has become one of the key approaches to promoting tissue regeneration. Traditional oxygen delivery strategies for tissue regeneration face several challenges, including inadequate sustained oxygen supply, poor targeting ability, and limited biocompatibility. To address these limitations, researchers have developed a variety of “intelligent oxygen delivery systems.” These systems can dynamically regulate oxygen release and achieve tissue-specific targeted delivery by responding to environmental or external stimuli, thereby significantly improving the precision and efficacy of oxygen therapy. This review systematically summarizes the biological functions of oxygen in tissue regeneration, with a particular focus on intelligent strategies for oxygen generation and supply developed in recent years. In addition, this review discusses the oxygen generation mechanisms, release kinetics, biocompatibility, application potential, and limitations of various oxygen delivery strategies. Finally, the review emphasizes that future designs of oxygen delivery systems should place greater emphasis on intelligent regulation, aiming to facilitate their clinical translation in tissue regeneration-related diseases such as chronic wounds, bone repair, and myocardial infarction.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115684"},"PeriodicalIF":17.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995210","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 : 2025-09-04DOI: 10.1016/j.addr.2025.115683
Junru Li , Yongming Han , Na Chen , Wenzhi Yang , Xiaohan Cai , Siqi Tian , Peipei Zhao , Wenhao Zhang , Dan Luo , Guoqing Tang , Fengqin Li , Peifeng Liu
DNA exhibits remarkable versatility, which is attributed to its inherent molecular recognition capabilities, programmable sequences, and excellent biocompatibility. Among its various topological forms, branched DNA (bDNA), including Y-shaped DNA (Y-DNA), X-shaped DNA (X-DNA), etc., stands out as a fundamental building block for fabricating functional DNA-based materials and has demonstrated great promise across diverse applications in recent years. Motivated by urgent demands in disease diagnosis and therapy, bDNA has developed into a rapidly advancing field. In this review, the design strategies for synthesizing monomers of bDNA and their assembly into complex functional materials are summarized. The pivotal role of bDNA in disease diagnostics is presented, emphasizing its utility in detecting disease-related biomarkers with high sensitivity and specificity. Additionally, we highlight the therapeutic applications of bDNA-based materials, such as hydrogels and microspheres, particularly in cancer treatment and the clinical translation of bDNA. Finally, the challenges and future directions for advancing bDNA technology in disease diagnosis and therapy are discussed, providing new insights into potential breakthroughs and their translational potential. These advances highlight the clinical translational potential of bDNA structures as powerful tools for disease diagnosis and treatment, offering promising avenues for improved disease detection and personalized therapy.
{"title":"Branched DNA for disease diagnosis and therapy","authors":"Junru Li , Yongming Han , Na Chen , Wenzhi Yang , Xiaohan Cai , Siqi Tian , Peipei Zhao , Wenhao Zhang , Dan Luo , Guoqing Tang , Fengqin Li , Peifeng Liu","doi":"10.1016/j.addr.2025.115683","DOIUrl":"10.1016/j.addr.2025.115683","url":null,"abstract":"<div><div>DNA exhibits remarkable versatility, which is attributed to its inherent molecular recognition capabilities, programmable sequences, and excellent biocompatibility. Among its various topological forms, branched DNA (bDNA), including Y-shaped DNA (Y-DNA), X-shaped DNA (X-DNA), etc., stands out as a fundamental building block for fabricating functional DNA-based materials and has demonstrated great promise across diverse applications in recent years. Motivated by urgent demands in disease diagnosis and therapy, bDNA has developed into a rapidly advancing field. In this review, the design strategies for synthesizing monomers of bDNA and their assembly into complex functional materials are summarized. The pivotal role of bDNA in disease diagnostics is presented, emphasizing its utility in detecting disease-related biomarkers with high sensitivity and specificity. Additionally, we highlight the therapeutic applications of bDNA-based materials, such as hydrogels and microspheres, particularly in cancer treatment and the clinical translation of bDNA. Finally, the challenges and future directions for advancing bDNA technology in disease diagnosis and therapy are discussed, providing new insights into potential breakthroughs and their translational potential. These advances highlight the clinical translational potential of bDNA structures as powerful tools for disease diagnosis and treatment, offering promising avenues for improved disease detection and personalized therapy.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115683"},"PeriodicalIF":17.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983297","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 : 2025-09-01DOI: 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}
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