Dingcheng Zhu , Dennis Brückner , Martin Sosniok , Marvin Skiba , Neus Feliu , Marta Gallego , Yang Liu , Florian Schulz , Gerald Falkenberg , Wolfgang J. Parak , Carlos Sanchez-Cano
{"title":"Size-dependent penetration depth of colloidal nanoparticles into cell spheroids","authors":"Dingcheng Zhu , Dennis Brückner , Martin Sosniok , Marvin Skiba , Neus Feliu , Marta Gallego , Yang Liu , Florian Schulz , Gerald Falkenberg , Wolfgang J. Parak , Carlos Sanchez-Cano","doi":"10.1016/j.addr.2025.115593","DOIUrl":"10.1016/j.addr.2025.115593","url":null,"abstract":"<div><div>The penetration of nanoparticle (NP)-based drugs into tissue is essential for their use as nanomedicines. Systematic studies about how different NP properties, such as size, influence NP penetration are helpful for the development of NP-based drugs. An overview of how NPs of different sizes may penetrate three-dimensional cell spheroids is given. In particular different techniques for experimental analysis are compared, including mass spectrometry, flow cytometry, optical fluorescence microscopy, X-ray fluorescence microscopy, and transmission electron microscopy. An experimental data set is supplemented exclusively made for this review, in which the results of different techniques are visualized. Limitations of the analysis techniques for different types of NPs, including carbon-based materials, are discussed.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115593"},"PeriodicalIF":15.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915491","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}
E.Coulter Montague , Bilgehan Ozcan , Elana Sefton , Fanny Wulkan , Faisal J. Alibhai , Michael A. Laflamme
{"title":"Human pluripotent stem cell-based cardiac repair: Lessons learned and challenges ahead","authors":"E.Coulter Montague , Bilgehan Ozcan , Elana Sefton , Fanny Wulkan , Faisal J. Alibhai , Michael A. Laflamme","doi":"10.1016/j.addr.2025.115594","DOIUrl":"10.1016/j.addr.2025.115594","url":null,"abstract":"<div><div>The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and hPSC-derived cardiac progenitors (hPSC-CPs) represents a promising strategy for regenerating hearts damaged by myocardial infarction (MI). After nearly two decades of experience testing these cell populations in various small- and large-animal MI models, multiple clinical trials have recently been initiated. In this review, we consider the principal lessons learned from preclinical experience with hPSC-CMs and -CPs, focusing on three conclusions that have been supported by the majority of reported transplantation studies. First, hPSC-CMs and -CPs stably engraft in injured hearts and partially remuscularize the infarct scar, but more progress is needed to improve graft cell retention and survival. Second, the transplantation of hPSC-CMs and -CPs has been found to improve contractile function in infarcted hearts, but the mechanistic basis for these effects remains incompletely elucidated. Third, the graft tissue formed by these cells can integrate and activate synchronously with host myocardium, but this capacity for electromechanical integration has been associated with an elevated risk of graft-related arrhythmias. Here, we summarize the preclinical evidence supporting these three observations, identify the relevant gaps and barriers to translation, and summarize ongoing efforts to improve the safety and efficacy of hPSC-CM- and -CP-based regenerative therapies.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115594"},"PeriodicalIF":15.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905543","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}
Zahra Rezaei , Niyou Wang , Yipei Yang , Kannan Govindaraj , Jose Joaquin Velasco , Alvaro Dario Martinez Blanco , Nam Ho Bae , HeaYeon Lee , Su Ryon Shin
{"title":"Enhancing organoid technology with carbon-based nanomaterial biosensors: Advancements, challenges, and future directions","authors":"Zahra Rezaei , Niyou Wang , Yipei Yang , Kannan Govindaraj , Jose Joaquin Velasco , Alvaro Dario Martinez Blanco , Nam Ho Bae , HeaYeon Lee , Su Ryon Shin","doi":"10.1016/j.addr.2025.115592","DOIUrl":"10.1016/j.addr.2025.115592","url":null,"abstract":"<div><div>Various carbon-based nanomaterials (CBNs) have been utilized to develop nano- and microscale biosensors that enable real-time and continuous monitoring of biochemical and biophysical changes in living biological systems. The integration of CBN-based biosensors into organoids has recently provided valuable insights into organoid development, disease modeling, and drug responses, enhancing their functionality and expanding their applications in diverse biomedical fields. These biosensors have been particularly transformative in studying neurological disorders, cardiovascular diseases, cancer progression, and liver toxicity, where precise, non-invasive monitoring is crucial for understanding pathophysiological mechanisms and assessing therapeutic efficacy. This review introduces intra- and extracellular biosensors incorporating CBNs such as graphene, carbon nanotubes (CNTs), graphene oxide (GO), reduced graphene oxide (rGO), carbon dots (CDs), and fullerenes. Additionally, it discusses strategies for improving the biocompatibility of CBN-based biosensors and minimizing their potential toxicity to ensure long-term organoid viability. Key challenges such as biosensor integration, data accuracy, and functional compatibility with specific organoid models are also addressed. Furthermore, this review highlights how CBN-based biosensors enhance the precision and relevance of organoid models in biomedical research, particularly in organ-specific applications such as brain-on-a-chip systems for neurodegenerative disease studies, liver-on-a-chip platforms for hepatotoxicity screening, and cardiac organoids for assessing cardiotoxicity in drug development. Finally, it explores how biosensing technologies could revolutionize personalized medicine by enabling high throughput drug screening, patient-specific disease modeling, and integrated sensing platforms for early diagnostics. By capturing current advancements and future directions, this review underscores the transformative potential of carbon-based nanotechnology in organoid research and its broader impact on medical science.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115592"},"PeriodicalIF":15.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905717","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}
Elena Totter , Emilie von Einsiedel , Lisa Regazzoni, Simone Schuerle
{"title":"Paving the way for bacteria-based drug delivery: biohybrid microrobots emerging from microrobotics and synthetic biology","authors":"Elena Totter , Emilie von Einsiedel , Lisa Regazzoni, Simone Schuerle","doi":"10.1016/j.addr.2025.115577","DOIUrl":"10.1016/j.addr.2025.115577","url":null,"abstract":"<div><div>Advances in microrobotics and synthetic biology are paving the way for innovative solutions to long-standing challenges in drug delivery. Both fields have independently worked on engineering bacteria as a therapeutic system, focusing on enhancing propulsion, cargo delivery, detection, and biocompatibility. Bacteria, with their inherent adaptability and functional versatility, serve as an ideal foundation for these efforts, enabling them to navigate complex biological environments such as the human body.</div><div>This review explores the convergence of microrobotics and synthetic biology, which has catalysed the development of biohybrid bacterial microrobots that integrate the strengths of both disciplines. By incorporating external control modalities – such as light, ultrasound, and magnetic fields – these hybrid systems address the limitations of purely microrobotic or biological approaches, offering new opportunities to enhance precision and efficacy in targeted therapies.</div><div>However, realising the full potential of biohybrid bacterial microrobots requires overcoming critical challenges, such as ensuring compatibility between biological and synthetic components, scaling manufacturing processes, and defining regulatory pathways tailored to living therapeutics. Addressing these hurdles through joint, interdisciplinary research efforts, can unlock the transformative possibilities of these systems in modern medicine.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115577"},"PeriodicalIF":15.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841108","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}
Yujin Lee , Hyun Gi Koh , Kyoung Heon Kim , Yong-Su Jin , Bong Hyun Sung , Jungyeon Kim
{"title":"Enhancing the persistence of engineered biotherapeutics in the gut: Adhesion, glycan metabolism, and environmental resistance","authors":"Yujin Lee , Hyun Gi Koh , Kyoung Heon Kim , Yong-Su Jin , Bong Hyun Sung , Jungyeon Kim","doi":"10.1016/j.addr.2025.115591","DOIUrl":"10.1016/j.addr.2025.115591","url":null,"abstract":"<div><div>Engineered live biotherapeutic products (eLBPs) are receiving increasing attention as next-generation therapeutics to treat a variety of diseases with high specificity and effectiveness. Despite their potential, eLBPs face challenges, such as limited colonization, competition with native microbiota, nutrient depletion, and susceptibility to gastrointestinal stresses, which ultimately reduce their persistence in the gut and hinder their therapeutic efficacy. This review examines the key strategies to enhance the persistence and activity of eLBPs in the gut environment. First, methods to strengthen the adhesion capacity of eLBPs are discussed, including genetic engineering to express adhesins and chemical surface modifications to improve their binding to mucus and epithelial cells. Second, strategies to improve the ability of eLBPs to efficiently use mucin-derived sugars, which are continuously secreted by intestinal epithelial cells, were highlighted. These strategies involve the introduction and optimization of glycan-degrading enzymes and metabolic pathways for key mucin sugars, such as N-acetylglucosamine, galactose, and sialic acid, to support sustained energy production and enhance gut colonization. Third, strategies to improve the resistance of eLBPs against environmental stress are discussed, including genetic modifications to stabilize cell membranes, enhancement of ion pump activity, overexpression of stress-response proteins, and encapsulation techniques to provide protection. The implementation of these strategies can address challenges related to gut colonization by eLBPs, thereby enhancing their metabolic activity and enabling sustained and efficient secretion of therapeutic molecules. This review offers a comprehensive framework for developing and optimizing eLBPs, paving the way for their successful clinical application with enhanced effectiveness in treating gastrointestinal and systemic diseases.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115591"},"PeriodicalIF":15.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841109","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}
Jiahua Zhang , Linjie Ma , Yong Hou , Haoyi Ouyang , Hyunsik Hong , Kanghyeon Kim , Heemin Kang , Zhiqin Chu
{"title":"Nanodiamond-Based Sensing: A revolution for biosensors in capturing elusive bio-signals in living cells","authors":"Jiahua Zhang , Linjie Ma , Yong Hou , Haoyi Ouyang , Hyunsik Hong , Kanghyeon Kim , Heemin Kang , Zhiqin Chu","doi":"10.1016/j.addr.2025.115590","DOIUrl":"10.1016/j.addr.2025.115590","url":null,"abstract":"<div><div>Cells constantly produce elusive bio-signals, such as cellular forces, free radicals, and molecular interactions, that are important for understanding diseases and treatment effects. However, detecting these signals is challenging because of issues with sensitivity, specificity, and the complexity of biological systems. Owing to their unique properties, nanodiamonds have emerged as a promising platform for detecting such elusive bio-signals, providing enhanced precision and effectiveness in diagnostics and therapies. In this review, we explore the detection of intracellular elusive bio-signals using nitrogen-vacancy (NV) centers in nanodiamonds, presenting case studies on their applications in cell force, free radicals, molecular interactions, and nanoscale thermometry. Moreover, we explore the design and applications of nanodiamonds as nanocarriers in quantum sensors and drug delivery systems.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115590"},"PeriodicalIF":15.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837503","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}
Jaehyun Lee , Sandra McClure , Ralph R. Weichselbaum , Mark Mimee
{"title":"Designing live bacterial therapeutics for cancer","authors":"Jaehyun Lee , Sandra McClure , Ralph R. Weichselbaum , Mark Mimee","doi":"10.1016/j.addr.2025.115579","DOIUrl":"10.1016/j.addr.2025.115579","url":null,"abstract":"<div><div>Humans are home to a diverse community of bacteria, many of which form symbiotic relationships with their host. Notably, tumors can also harbor their own unique bacterial populations that can influence tumor growth and progression. These bacteria, which selectively colonize hypoxic and acidic tumor microenvironments, present a novel therapeutic strategy to combat cancer. Advancements in synthetic biology enable us to safely and efficiently program therapeutic drug production in bacteria, further enhancing their potential. This review provides a comprehensive guide to utilizing bacteria for cancer treatment. We discuss key considerations for selecting bacterial strains, emphasizing their colonization efficiency, the delicate balance between safety and anti-tumor efficacy, and the availability of tools for genetic engineering. We also delve into strategies for precise spatiotemporal control of drug delivery to minimize adverse effects and maximize therapeutic impact, exploring recent examples of engineered bacteria designed to combat tumors. Finally, we address the underlying challenges and future prospects of bacterial cancer therapy. This review underscores the versatility of bacterial therapies and outlines strategies to fully harness their potential in the fight against cancer.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115579"},"PeriodicalIF":15.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"hPSC-based treatment of retinal diseases – Current progress and challenges","authors":"Atsuta Ozaki , Daiki Sakai , Michiko Mandai","doi":"10.1016/j.addr.2025.115587","DOIUrl":"10.1016/j.addr.2025.115587","url":null,"abstract":"<div><div>Degenerative retinal diseases, such as age-related macular degeneration (AMD) and inherited retinal diseases (IRDs), cause visual impairment due to irreversible damage to the retinal pigment epithelium (RPE) and photoreceptor cells (PRCs). Currently, no definitive treatment exists. However, cell-based therapies using induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) offer potential solutions for restoring damaged retinal cells. This review summarizes recent advances in RPE and PRC transplantation, highlighting the benefits of each approach. For RPE transplantation, we focus on the outcomes of clinical studies involving three formulations: RPE sheets, RPE suspensions, and RPE strips. In the context of PRC transplantation, we trace the progress from fetal retinal transplantation to the latest studies. Additionally, we discuss our recent clinical work with retinal sheet transplantation and genome-edited retinal organoid sheets, which aim to improve functional integration by reducing bipolar cells in grafts. Finally, with the overall safety of the regenerative cell-based therapies demonstrated in past clinical applications, we explore future prospects for these therapies.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115587"},"PeriodicalIF":15.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Be a GEM: Biocontained, environmentally applied, genetically engineered microbes","authors":"Tae Seok Moon","doi":"10.1016/j.addr.2025.115578","DOIUrl":"10.1016/j.addr.2025.115578","url":null,"abstract":"<div><div>Technological advances in engineering biology or synthetic biology have enabled practical applications of genetically engineered microbes (GEMs), including their use as living diagnostics and vehicles for therapeutics. However, technological and non-technological issues associated with biocontainment of GEMs have yet to be addressed before fully realizing their potential. In this short perspective, I briefly discuss the relevant technologies for GEM biocontainment as well as environmental impacts, regulatory issues, and public perception of GEMs.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"221 ","pages":"Article 115578"},"PeriodicalIF":15.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822658","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}
Sepideh Khoshnevis , Michael H. Smolensky , Shahab Haghayegh
{"title":"Circadian attributes of neurological and psychiatric disorders as basis for their medication chronotherapy","authors":"Sepideh Khoshnevis , Michael H. Smolensky , Shahab Haghayegh","doi":"10.1016/j.addr.2025.115576","DOIUrl":"10.1016/j.addr.2025.115576","url":null,"abstract":"<div><div>This review focuses on (i) 24 h patterns in the symptom intensity of common neurologic and psychiatric disorders and (ii) medications prescribed for their management that have a recommended administration time or schedule, presumably to potentiate desired and minimize undesired effects and by definition qualify them as chronotherapies. Predictable-in-time patterning of symptoms is exhibited by many neurologic –– headaches, multiple sclerosis, neurogenic orthostatic hypotension, neuropathic pain, Parkinson’s disease, epileptic seizure, attention deficit hyperactivity, Alzheimer’s disease – and psychiatric – eating, depressive, obsessive–compulsive, post-traumatic stress, anxiety, and panic – disorders, due either to circadian rhythms of disease pathophysiology or inadequacies of medication-delivery systems. Circadian disruption and circadian misalignment of the sleep-wake and other 24 h rhythms plus late chronotype are characteristic of many of these disorders, suggesting involvement in the mechanisms or consequence of their pathology or as an adverse effect of therapy, especially when administered at an inappropriate biological time. The Prescribers’ Digital Reference, a compendium of all prescription medications approved for marketing in the US, reveals 65 of them are utilized to manage neurologic and psychiatric disorders by a specified time-of-day or an asymmetrical interval or strength of dose schedule, presumably to optimize beneficial and minimize adverse effects, thereby qualifying them as chronotherapies. Overall, the contents of this review are intended to inform the development of future chronotherapies that incorporate state-of-the-art drug-delivery systems to improve management of neurologic and psychiatric disorders and associated circadian malalignment and disruption.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"223 ","pages":"Article 115576"},"PeriodicalIF":15.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776029","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}