Pub Date : 2025-08-05DOI: 10.1016/j.addr.2025.115661
Zhengqing Zhou, Irida Shyti, Jaemin Kim, Lingchong You
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.
{"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}
Pub Date : 2025-07-30DOI: 10.1016/j.addr.2025.115660
Dandan Li , Huarui Liu , Xintong Li , Changping Yang , Hanyin Zhu , Hong Wang , Jianbing Liu , Baoquan Ding
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 in vivo immunotherapy are discussed.
{"title":"Applications of DNA-based nanostructures in immunotherapy","authors":"Dandan Li , Huarui Liu , Xintong Li , Changping Yang , Hanyin Zhu , Hong Wang , Jianbing Liu , 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}
Carbon dots (CDs), a class of carbonaceous and fluorescent nanomaterials with ultra-small dimensions (below 10 nm), have become popular nanoparticles in several fields, such as nanomedicine, catalysis, sensing or electronics. Due to their chemical versatility, luminescence, surface functional groups, biocompatibility and water solubility, they have been extensively studied in biomedical field. In this review, we focused on CDs used as nano contrast agents (nCAs) for fluorescence, magnetic resonance or computed tomography imaging in small animal models. We described the advantages of using CDs, highlighting some relevant examples, as well as the current issues that slow down their effective use in biomedicine, such as the rational synthetic design, scant purification and poor characterization. Lastly, we gathered some perspectives to develop carbon dots with more reliable properties and accomplish cutting-edge applications.
{"title":"Carbon dots as multi-modal contrast agents: opportunities and open challenges for in vivo bioimaging","authors":"Elisa Sturabotti , Beatriz Sierra-Serrano , Samantha Marcelino Apresto , Michele Cesco , Luca Comparini , Lucia Cardo , Maurizio Prato","doi":"10.1016/j.addr.2025.115659","DOIUrl":"10.1016/j.addr.2025.115659","url":null,"abstract":"<div><div>Carbon dots (CDs), a class of carbonaceous and fluorescent nanomaterials with ultra-small dimensions (below 10 nm), have become popular nanoparticles in several fields, such as nanomedicine, catalysis, sensing or electronics. Due to their chemical versatility, luminescence, surface functional groups, biocompatibility and water solubility, they have been extensively studied in biomedical field. In this review, we focused on CDs used as nano contrast agents (nCAs) for fluorescence, magnetic resonance or computed tomography imaging in small animal models. We described the advantages of using CDs, highlighting some relevant examples, as well as the current issues that slow down their effective use in biomedicine, such as the rational synthetic design, scant purification and poor characterization. Lastly, we gathered some perspectives to develop carbon dots with more reliable properties and accomplish cutting-edge applications.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115659"},"PeriodicalIF":15.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-22DOI: 10.1016/j.addr.2025.115658
Baishali Kanjilal , Prince David Okoro , Razieh Jaberi , Ashley Taepakdee , Nourouddin Sharifi , Joshua Morgan , Vijayalakshmi Santhakumar , Victor G. Rodgers , Arameh Masoumi , Iman Noshadi
Carbon‐based nanomaterials (CBMs) and their polymeric composites have garnered widespread interest in treating neurotrauma and neurodegenerative diseases, where restoring damaged central and peripheral nervous systems remains a persistent clinical challenge. These materials provide exceptional electrical conductivity, mechanical robustness, and tunable nanoscale architectures conducive to guiding neuronal growth, synaptic connectivity, and targeted biomolecule delivery. In this review, we explore the rationale, recent advances, and translational potential of CBM scaffolds in promoting neuronal survival, neurite outgrowth, and functional maturity across various experimental models. We detail key fabrication strategies, including electrospinning, phase inversion, 3D bioprinting, and pyrolysis that enable precise control over scaffolds’ structural and mechanical properties while facilitating the incorporation of neurotrophic factors, genes, and therapeutic drugs. Emerging in vivo findings suggest that CBM nanocomposites promote regenerative outcomes in peripheral nerve injuries at levels comparable to, or exceeding conventional autografts, underscoring their promise as off‐the‐shelf solutions. Nonetheless, concerns persist regarding large-scale manufacturing, cytotoxicity, and meeting regulatory standards for clinical use. By highlighting cutting-edge innovations and remaining bottlenecks, this review aims to guide future research endeavors in harnessing CBM scaffolds for safe and effective neural tissue repair.
{"title":"Advances in carbon nanomaterials and their polymeric composites in neural tissue engineering","authors":"Baishali Kanjilal , Prince David Okoro , Razieh Jaberi , Ashley Taepakdee , Nourouddin Sharifi , Joshua Morgan , Vijayalakshmi Santhakumar , Victor G. Rodgers , Arameh Masoumi , Iman Noshadi","doi":"10.1016/j.addr.2025.115658","DOIUrl":"10.1016/j.addr.2025.115658","url":null,"abstract":"<div><div>Carbon‐based nanomaterials (CBMs) and their polymeric composites have garnered widespread interest in treating neurotrauma and neurodegenerative diseases, where restoring damaged central and peripheral nervous systems remains a persistent clinical challenge. These materials provide exceptional electrical conductivity, mechanical robustness, and tunable nanoscale architectures conducive to guiding neuronal growth, synaptic connectivity, and targeted biomolecule delivery. In this review, we explore the rationale, recent advances, and translational potential of CBM scaffolds in promoting neuronal survival, neurite outgrowth, and functional maturity across various experimental models. We detail key fabrication strategies, including electrospinning, phase inversion, 3D bioprinting, and pyrolysis that enable precise control over scaffolds’ structural and mechanical properties while facilitating the incorporation of neurotrophic factors, genes, and therapeutic drugs. Emerging <em>in vivo</em> findings suggest that CBM nanocomposites promote regenerative outcomes in peripheral nerve injuries at levels comparable to, or exceeding conventional autografts, underscoring their promise as off‐the‐shelf solutions. Nonetheless, concerns persist regarding large-scale manufacturing, cytotoxicity, and meeting regulatory standards for clinical use. By highlighting cutting-edge innovations and remaining bottlenecks, this review aims to guide future research endeavors in harnessing CBM scaffolds for safe and effective neural tissue repair.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115658"},"PeriodicalIF":17.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-20DOI: 10.1016/j.addr.2025.115657
Sara Jamshidi Parvar , Cheng In Wong , Andrew Lewis , Elwira Szychot , Christopher J. Morris , David Shorthouse , Karolina Dziemidowicz
The blood–brain barrier’s protective nature greatly restricts the entrance of active pharmaceutical ingredients (APIs), presenting a significant challenge for effective drug delivery into the brain. Convection-enhanced delivery (CED) is emerging as a promising strategy to overcome this barrier by enabling the direct infusion of APIs at therapeutic concentrations into brain tissue, thereby expanding potential treatment options for brain tumours and neurological conditions. This review provides a current and comprehensive update on the field of CED, highlighting recent advances and ongoing challenges. In addition, various formulation strategies, including nanoparticles, cyclodextrins, and hydrogels, are considered, with an emphasis on identifying optimal formulation properties required to enhance CED administration. With insights from clinical trials, device engineering and pharmaceutical perspectives, this review highlights the critical factors that influence the success of CED and outlines future directions for its effective clinical translation.
{"title":"Convection-enhanced delivery for brain malignancies: Technical parameters, formulation strategies and clinical perspectives","authors":"Sara Jamshidi Parvar , Cheng In Wong , Andrew Lewis , Elwira Szychot , Christopher J. Morris , David Shorthouse , Karolina Dziemidowicz","doi":"10.1016/j.addr.2025.115657","DOIUrl":"10.1016/j.addr.2025.115657","url":null,"abstract":"<div><div>The blood–brain barrier’s protective nature greatly restricts the entrance of active pharmaceutical ingredients (APIs), presenting a significant challenge for effective drug delivery into the brain. Convection-enhanced delivery (CED) is emerging as a promising strategy to overcome this barrier by enabling the direct infusion of APIs at therapeutic concentrations into brain tissue, thereby expanding potential treatment options for brain tumours and neurological conditions. This review provides a current and comprehensive update on the field of CED, highlighting recent advances and ongoing challenges. In addition, various formulation strategies, including nanoparticles, cyclodextrins, and hydrogels, are considered, with an emphasis on identifying optimal formulation properties required to enhance CED administration. With insights from clinical trials, device engineering and pharmaceutical perspectives, this review highlights the critical factors that influence the success of CED and outlines future directions for its effective clinical translation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115657"},"PeriodicalIF":15.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664351","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 : 2025-07-17DOI: 10.1016/j.addr.2025.115656
Konstantinos Loukelis , Udayabhanu Jammalamadaka , Antonios G. Mikos
Over the years, sustained research into the role of biomolecules in bone regeneration has provided valuable insights into their potential as therapeutic agents for tissue growth. However, challenges such as short half-lives and high production costs underscore the need for advanced tissue engineering platforms. Precise spatial delivery of these biomolecules to target sites remains a critical requirement. 3D printing has emerged as a powerful technology, enabling the layer-by-layer fabrication of hierarchically complex 3D structures with tailored biomechanical properties. Additionally, it facilitates the preservation and delivery of bioactive molecules following desirable kinetic patterns. This review highlights the most recent and notable advancements of 3D printing-enabled spatial patterning of biological cues aimed at promoting the formation of bone tissue, vascularized bone, osteochondral tissue, and bone-tendon interface.
{"title":"3D printing-enabled spatial patterning of biomimetic signals for bone tissue engineering","authors":"Konstantinos Loukelis , Udayabhanu Jammalamadaka , Antonios G. Mikos","doi":"10.1016/j.addr.2025.115656","DOIUrl":"10.1016/j.addr.2025.115656","url":null,"abstract":"<div><div>Over the years, sustained research into the role of biomolecules in bone regeneration has provided valuable insights into their potential as therapeutic agents for tissue growth. However, challenges such as short half-lives and high production costs underscore the need for advanced tissue engineering platforms. Precise spatial delivery of these biomolecules to target sites remains a critical requirement. 3D printing has emerged as a powerful technology, enabling the layer-by-layer fabrication of hierarchically complex 3D structures with tailored biomechanical properties. Additionally, it facilitates the preservation and delivery of bioactive molecules following desirable kinetic patterns. This review highlights the most recent and notable advancements of 3D printing-enabled spatial patterning of biological cues aimed at promoting the formation of bone tissue, vascularized bone, osteochondral tissue, and bone-tendon interface.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115656"},"PeriodicalIF":15.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652217","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 : 2025-07-17DOI: 10.1016/j.addr.2025.115655
Mrutyunjaya Panda , Maria Fakitsa , Maria Markaki , Nektarios Tavernarakis
An increase in the aging population is accompanied by increased susceptibility to age-associated neurodegeneration, with currently no cure. Despite the diversity of symptoms and etiologies, neurodegenerative disorders share mechanistic commonalities and many pathophysiological features. These include disruptions in circadian rhythms that affect neuronal physiology. Systematic investigations in several animal models have advanced our understanding of the molecular processes that link circadian rhythms and neurodegenerative disease states. These models have also been used to screen and validate promising chronotherapeutic drug candidates that target the circadian clock to ameliorate neurodegeneration. With the emergence of robust and reliable methodologies to measure daily rhythms, the nematode model Caenorhabditis elegans has become a versatile tool for high throughput chronotherapeutic drug screening against neurodegenerative disorders. In this review, we discuss the unique features and advantages of C. elegans as an enabling platform for chronotherapeutic drug discovery, towards the development of innovative strategies for the treatment of human neurodegenerative conditions.
{"title":"Caenorhabditis elegans as an emerging high throughput chronotherapeutic drug screening platform for human neurodegenerative disorders","authors":"Mrutyunjaya Panda , Maria Fakitsa , Maria Markaki , Nektarios Tavernarakis","doi":"10.1016/j.addr.2025.115655","DOIUrl":"10.1016/j.addr.2025.115655","url":null,"abstract":"<div><div>An increase in the aging population is accompanied by increased susceptibility to age-associated neurodegeneration, with currently no cure. Despite the diversity of symptoms and etiologies, neurodegenerative disorders share mechanistic commonalities and many pathophysiological features. These include disruptions in circadian rhythms that affect neuronal physiology. Systematic investigations in several animal models have advanced our understanding of the molecular processes that link circadian rhythms and neurodegenerative disease states. These models have also been used to screen and validate promising chronotherapeutic drug candidates that target the circadian clock to ameliorate neurodegeneration. With the emergence of robust and reliable methodologies to measure daily rhythms, the nematode model <em>Caenorhabditis elegans</em> has become a versatile tool for high throughput chronotherapeutic drug screening against neurodegenerative disorders. In this review, we discuss the unique features and advantages of <em>C. elegans</em> as an enabling platform for chronotherapeutic drug discovery, towards the development of innovative strategies for the treatment of human neurodegenerative conditions.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115655"},"PeriodicalIF":15.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645548","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 : 2025-07-12DOI: 10.1016/j.addr.2025.115653
Adam Campbell-Galland , Akanksha Bafna , Aarti Jagannath
Circadian rhythms are intrinsic biological processes in all forms of life, governed by a molecular clock, organising physiological and behavioural cycles to align with a 24-hour light–dark cycle. The disruption of these rhythms has been linked to a plethora of neurological conditions and impacting cognitive and metabolic functions.
This review offers a clear overview of the genetic and molecular mechanisms that govern the circadian clock. It focuses on the core clock feedback loops, the pathways involved and how these mechanisms are regulated. We explore how clocks in peripheral tissues are synchronised to the suprachiasmatic nucleus and how this is achieved through neuronal and humoral pathways. Additionally, we discuss how dysregulation in circadian rhythms contribute to neurological conditions and potential therapeutic treatments targeting circadian mechanisms. Understanding the mechanisms of circadian dysregulation provides insight into disease pathology and potential therapies. Interventions targeting circadian mechanisms, such as gene and drug delivery systems, show promise to restore rhythms and mitigate neurological symptoms. This review collates current knowledge on circadian biology and its applications addressing neurological dysfunctions, providing a foundation for potential chronotherapeutic interventions.
{"title":"The molecular circadian clock: From fundamental mechanisms to therapeutic promise in neurological disorders","authors":"Adam Campbell-Galland , Akanksha Bafna , Aarti Jagannath","doi":"10.1016/j.addr.2025.115653","DOIUrl":"10.1016/j.addr.2025.115653","url":null,"abstract":"<div><div>Circadian rhythms are intrinsic biological processes in all forms of life, governed by a molecular clock, organising physiological and behavioural cycles to align with a 24-hour light–dark cycle. The disruption of these rhythms has been linked to a plethora of neurological conditions and impacting cognitive and metabolic functions.</div><div>This review offers a clear overview of the genetic and molecular mechanisms that govern the circadian clock. It focuses on the core clock feedback loops, the pathways involved and how these mechanisms are regulated. We explore how clocks in peripheral tissues are synchronised to the suprachiasmatic nucleus and how this is achieved through neuronal and humoral pathways. Additionally, we discuss how dysregulation in circadian rhythms contribute to neurological conditions and potential therapeutic treatments targeting circadian mechanisms. Understanding the mechanisms of circadian dysregulation provides insight into disease pathology and potential therapies. Interventions targeting circadian mechanisms, such as gene and drug delivery systems, show promise to restore rhythms and mitigate neurological symptoms. This review collates current knowledge on circadian biology and its applications addressing neurological dysfunctions, providing a foundation for potential chronotherapeutic interventions.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115653"},"PeriodicalIF":17.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-11DOI: 10.1016/j.addr.2025.115648
Georgina B Armstrong , Harriet Graham , Anthony Cheung , Hanieh Montaseri , Glenn A Burley , Sophia N Karagiannis , Zahra Rattray
Antibody-drug conjugates (ADCs) are rapidly emerging as an effective multimodal approach for the targeted delivery of cytotoxic small molecules to tumours with aberrantly overexpressed markers. Recent advances in antibody engineering and the emergence of highly potent cytotoxic drugs have created unprecedented scope for precision-based design of novel ADCs against chemotherapy-resistant tumours. However, their clinical translation faces the challenge of balancing efficacy and toxicity. Innovations in conjugation chemistries and antibody engineering are addressing these challenges, yet a more comprehensive in vitro − in vivo correlation is critical to accelerating their clinical translation. This review examines the latest advancements in ADC-based therapies for hard-to-treat cancers, focusing on design considerations that define their efficacy in breast cancer and glioblastoma multiforme. Additionally, we highlight current challenges in reconciling ADC quality attributes influencing their in vivo performance, which impedes their clinical translation. By integrating cutting-edge advancements in antibody engineering with industrial insights, this review casts a spotlight on the pivotal role of ADCs as a powerful biomolecular toolbox for delivering next-generation therapies to address unmet clinical need.
{"title":"Antibody-drug conjugates as multimodal therapies against hard-to-treat cancers","authors":"Georgina B Armstrong , Harriet Graham , Anthony Cheung , Hanieh Montaseri , Glenn A Burley , Sophia N Karagiannis , Zahra Rattray","doi":"10.1016/j.addr.2025.115648","DOIUrl":"10.1016/j.addr.2025.115648","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) are rapidly emerging as an effective multimodal approach for the targeted delivery of cytotoxic small molecules to tumours with aberrantly overexpressed markers. Recent advances in antibody engineering and the emergence of highly potent cytotoxic drugs have created unprecedented scope for precision-based design of novel ADCs against chemotherapy-resistant tumours. However, their clinical translation faces the challenge of balancing efficacy and toxicity. Innovations in conjugation chemistries and antibody engineering are addressing these challenges, yet a more comprehensive <em>in vitro − in vivo</em> correlation is critical to accelerating their clinical translation. This review examines the latest advancements in ADC-based therapies for hard-to-treat cancers, focusing on design considerations that define their efficacy in breast cancer and glioblastoma multiforme. Additionally, we highlight current challenges in reconciling ADC quality attributes influencing their <em>in vivo</em> performance, which impedes their clinical translation. By integrating cutting-edge advancements in antibody engineering with industrial insights, this review casts a spotlight on the pivotal role of ADCs as a powerful biomolecular toolbox for delivering next-generation therapies to address unmet clinical need.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115648"},"PeriodicalIF":15.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602876","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 : 2025-07-10DOI: 10.1016/j.addr.2025.115654
Gizem D. Ozdemir , Carolina dos Anjos , Mehmet A. Ozdemir , Leon G. Leanse , Tianhong Dai
The rise of antimicrobial resistance (AMR) poses a significant threat to global health, as traditional antimicrobials are increasingly losing efficacy against a broad spectrum of pathogens. Antimicrobial blue light (aBL), an innovative light-based approach that utilizes wavelengths between 405 and 470 nm, has emerged as a prominent alternative. Unlike conventional antimicrobials, aBL inactivates microorganisms without promoting resistance by targeting endogenous chromophores within pathogens to generate reactive oxygen species (ROS). This review first provides an in-depth analysis of aBL’s mechanisms of action, highlighting its unique ROS-driven effects on microbial membranes, DNA, and proteins. Moreover, we discussed recent developments in aBL’s applications across bacterial, viral, and fungal pathogens and evaluated its effectiveness in biofilm eradication and combinational therapies with conventional antimicrobials as well as with multimodal innovations. This review also examines the safety and regulatory considerations associated with aBL. While aBL holds tremendous potential, challenges remain in its clinical translation, including optimizing dosages, ensuring safety in complex biological systems, and advancing device design. Future research must address these gaps to facilitate the clinical translation of aBL and expand its role in combating resistant infections.
{"title":"Lights out for Superbugs: Is antimicrobial blue light a potential approach for future infection Control?","authors":"Gizem D. Ozdemir , Carolina dos Anjos , Mehmet A. Ozdemir , Leon G. Leanse , Tianhong Dai","doi":"10.1016/j.addr.2025.115654","DOIUrl":"10.1016/j.addr.2025.115654","url":null,"abstract":"<div><div>The rise of antimicrobial resistance (AMR) poses a significant threat to global health, as traditional antimicrobials are increasingly losing efficacy against a broad spectrum of pathogens. Antimicrobial blue light (aBL), an innovative light-based approach that utilizes wavelengths between 405 and 470 nm, has emerged as a prominent alternative. Unlike conventional antimicrobials, aBL inactivates microorganisms without promoting resistance by targeting endogenous chromophores within pathogens to generate reactive oxygen species (ROS). This review first provides an in-depth analysis of aBL’s mechanisms of action, highlighting its unique ROS-driven effects on microbial membranes, DNA, and proteins. Moreover, we discussed recent developments in aBL’s applications across bacterial, viral, and fungal pathogens and evaluated its effectiveness in biofilm eradication and combinational therapies with conventional antimicrobials as well as with multimodal innovations. This review also examines the safety and regulatory considerations associated with aBL. While aBL holds tremendous potential, challenges remain in its clinical translation, including optimizing dosages, ensuring safety in complex biological systems, and advancing device design. Future research must address these gaps to facilitate the clinical translation of aBL and expand its role in combating resistant infections.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115654"},"PeriodicalIF":15.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602877","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：