Shaobo Yang, Mengdi Yang, Maria Jennings, Hania Timek, Amber E. Haley, Rizwan Romee, Jiahe Li
{"title":"Repurposing the bacterial surface display technology for drug delivery","authors":"Shaobo Yang, Mengdi Yang, Maria Jennings, Hania Timek, Amber E. Haley, Rizwan Romee, Jiahe Li","doi":"10.1016/j.addr.2025.115701","DOIUrl":"https://doi.org/10.1016/j.addr.2025.115701","url":null,"abstract":"Bacteria have emerged as versatile platforms for therapeutic delivery, owing to their inherent adaptability, genetic tractability, and ability to interface with the human microbiome and immune system. This review explores the evolution of bacterial engineering for medical applications, emphasizing drug delivery strategies enabled by bacterial surface display technologies. We outline the advantages of surface display—such as enhanced localization, prolonged therapeutic activity, and reduced systemic toxicity—over conventional bacterial secretion and lysis-based delivery methods. The review details key biological mechanisms of surface display in both Gram-negative and Gram-positive bacteria, including outer membrane proteins, sortase-mediated anchoring, and spore-based systems. We also highlight emerging applications of surface-displayed cytokines, nanobodies, and immunomodulatory proteins in cancer therapy, vaccine development, microbiome engineering, and animal health. Innovative approaches combining bacterial display with conjugation systems and biosensors expand the potential of these living therapeutics for precise, responsive, and programmable interventions. Furthermore, we propose a future roadmap that leverages computational tools such as AlphaFold and in silico screening to rationally identify optimal outer membrane anchors, accelerating the design of next-generation surface display platforms. While challenges remain—including regulatory hurdles and microbial stability—continued interdisciplinary innovation with synthetic biology promises to transform engineered bacteria into clinically viable therapeutic agents. This review positions bacterial surface display as a powerful and underexplored modality for targeted drug delivery, bridging synthetic biology, immune engineering, and translational medicine.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"111 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216059","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}
Tanya Chhibber, Dekker C. Deacon, Hamidreza Ghandehari, Robert L. Judson-Torres
{"title":"Recent advances in gene delivery for melanocyte-associated disorders","authors":"Tanya Chhibber, Dekker C. Deacon, Hamidreza Ghandehari, Robert L. Judson-Torres","doi":"10.1016/j.addr.2025.115703","DOIUrl":"https://doi.org/10.1016/j.addr.2025.115703","url":null,"abstract":"Melanocytes are cells present at the epidermal-dermal junction of the skin that produce pigment melanin, which provides color to the skin, eyes, and hair. Dysregulation in melanocyte function, viability, or differentiation can result in melanocyte-associated disorders that can be broadly classified based on etiology as melanocyte hyperproliferation and hyperactivation, defects in melanin synthesis, inflammatory alterations in melanin production/trafficking, melanocyte destruction, and defects in melanocyte migration. While most of these disorders are of benign origin, the cosmetic implications of these conditions are associated with significant psychosocial burden and cultural stigma, having a significant impact on affected individuals. These conditions are primarily driven by changes in underlying gene expression (both at the genetic and epigenetic levels). Targeting the underlying genetic and transcriptomic changes in melanocyte-associated disorders using gene replacement (plasmid DNA, mRNA), gene knockdown (siRNA), or miRNA replacement (miRNA) presents a promising strategy for developing treatments for these conditions. The delivery of naked nucleic acid molecules is challenging, and lipid- and polymer-based particles have been widely evaluated for the successful delivery of biologically active nucleic acids to the melanocytes. This review provides an overview of melanocyte-associated pigmentary disorders and their underlying genetic factors and examines current preclinical and clinical efforts using non-viral polymeric and lipid-based delivery systems for plasmid DNA and RNA-based therapeutics.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"105 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216057","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}
Kurt D. Ristroph, Nathalie M. Pinkerton, Chester E. Markwalter, Suzanne M. D'Addio, Marian E. Gindy, Robert F. Pagels
{"title":"20 years of flash nanoprecipitation – from controlled precipitation to global medicine","authors":"Kurt D. Ristroph, Nathalie M. Pinkerton, Chester E. Markwalter, Suzanne M. D'Addio, Marian E. Gindy, Robert F. Pagels","doi":"10.1016/j.addr.2025.115700","DOIUrl":"https://doi.org/10.1016/j.addr.2025.115700","url":null,"abstract":"In the twenty years since the development of Flash NanoPrecipitation (FNP) technology, an antisolvent precipitation technique that uses rapid turbulent mixing to drive self-assembly of polymeric or lipid nanoparticles, the platform has been used for a wide variety of drug delivery applications in research and industry – most notably as the enabling technology for the global manufacture of the Pfizer-BioNTech COMIRNATY® mRNA lipid nanoparticle vaccine against SARS-CoV-2. Importantly, this makes FNP the only publicly-known manufacturing technology for global commercial-scale lipid nanoparticle formulation. This situation makes the technique remarkable and noteworthy and worth discussing broadly, which this article aims to do. It also sets FNP mixing as the benchmark technology against which other LNP manufacturing processes should be compared. Here we review the principles underpinning this continuous antisolvent precipitation technique, its scalability and use with downstream unit operations, and its utility in nanomedicine research. We discuss the current intellectual property landscape surrounding FNP technology and give examples of its industrial implementation for SARS-CoV-2 and low-cost antimalarial formulations. We end with a survey on recent improvements and extensions to the platform that enable the encapsulation of new classes of molecules and greater flexibility in manufacturing as FNP moves into its third decade.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"75 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203245","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":"Towards airway microbiome engineering for improving respiratory health.","authors":"Kelsey E Hern, Arthur Prindle","doi":"10.1016/j.addr.2025.115662","DOIUrl":"10.1016/j.addr.2025.115662","url":null,"abstract":"<p><p>The known roles of human-associated microbes in health and disease have expanded in recent years. While the gut microbiome is the most well studied, the airway microbiome is gaining attention as an important gatekeeper of respiratory health. Compared to the gut, the airway microbiome has lower species complexity, greater niche stability, and represents an immediate point of contact with the outside world. These features make it an attractive target for improving respiratory health. As respiratory disease continues to increase among humans, it will be critical to develop novel approaches to combat new and emergent bacterial infections, viruses, and cancers for which we do not currently have treatments. This review seeks to define strategies for airway microbiome engineering-the intentional manipulation of airway associated microbes to restore species balance, enhance protective functions, or treat disease. We summarize the growing body of literature linking the airway microbiome to respiratory health and discuss both broad-spectrum and high precision technologies that hold particular promise for further development. We argue that inhaled probiotics and bacteriophage are among the most attractive technologies for clinical translation of airway microbiome engineering to improve respiratory health.</p>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":" ","pages":"115662"},"PeriodicalIF":17.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glioblastoma and blood-brain barrier cell interplay in vitro models for stratification of drug efficacy","authors":"Cecília Ferreira, Bruno Sarmento, Cláudia Martins","doi":"10.1016/j.addr.2025.115702","DOIUrl":"https://doi.org/10.1016/j.addr.2025.115702","url":null,"abstract":"Glioblastoma (GBM) is the most lethal brain cancer in adults, with a dismal prognosis and no curative therapies available. The treatment landscape remains largely stagnant, relying on tumor resection, temozolomide (TMZ) chemotherapy, and radiotherapy, which are hampered by the blood-brain barrier (BBB) that limits drug blood-to-brain permeability and, consequently, therapeutic efficacy. Over 98 % of potential therapeutic candidates fail to penetrate the BBB, significantly contributing to the high recurrence rates of GBM. The urgent need for improved drug delivery strategies is compounded by the limitations of current preclinical models, which often inadequately mimic the complex BBB-GBM interaction. This review discusses recent advancements in the development of <em>in vitro</em> models that accurately replicate the BBB and GBM interplay, ranging from simplified two-dimensional (2D) systems to sophisticated three-dimensional (3D) constructs. Innovations such as microfluidic devices and multicellular spheroid cultures are highlighted as promising methods to enhance physiological relevance and predictive value in drug testing. By emphasizing the interplay between GBM and its microenvironment with the BBB, these models aim to accelerate the discovery and efficacy testing of novel anti-GBM agents. Ultimately, this review underscores the critical need for more representative <em>in vitro</em> platforms that not only reduce reliance on animal models but also adhere to the principles of the 3Rs (replacement, reduction, refinement) in biomedical research, paving the way for more effective therapeutic interventions against GBM.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"37 1","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194952","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}
Valery V. Tuchin , Tianhong Dai , Luís M. Oliveira
{"title":"Optical technologies in monitoring mobility and delivery of drugs and metabolic agents1","authors":"Valery V. Tuchin , Tianhong Dai , Luís M. Oliveira","doi":"10.1016/j.addr.2025.115699","DOIUrl":"10.1016/j.addr.2025.115699","url":null,"abstract":"","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"226 ","pages":"Article 115699"},"PeriodicalIF":17.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153606","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}
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
{"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}
Marta Łaszcz, Magdalena Urbanowicz, Ewelina Baran, Piotr Kulinowski
{"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":"https://doi.org/10.1016/j.addr.2025.115698","url":null,"abstract":"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.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"18 1","pages":""},"PeriodicalIF":16.1,"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}
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
{"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}
{"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}