Advanced drug delivery reviews最新文献

{"title":"CRISPR/Cas bioimaging: From whole body biodistribution to single-cell dynamics","authors":"Ekaterina Kolesova ,&nbsp;Sabina Pulone ,&nbsp;Dmitry Kostyushev ,&nbsp;Ennio Tasciotti","doi":"10.1016/j.addr.2025.115619","DOIUrl":"10.1016/j.addr.2025.115619","url":null,"abstract":"<div><div>This review explores the transformative role of CRISPR/Cas systems in optical bioimaging, emphasizing how advancements in nanoparticle (NP) technologies are revolutionizing the visualization of gene-editing processes both <em>in vitro</em> and <em>in vivo</em>. Optical imaging techniques, such as near-infrared (NIR) and fluorescence imaging, have greatly benefited from the integration of nanoformulated contrast agents, improving resolution, sensitivity, and specificity. CRISPR/Cas systems, originally developed just for gene editing, are now being coupled with these imaging modalities to enable real-time monitoring and quantitative measurements of metabolites, vitamins, proteins, nucleic acids and other entities in specific areas of the body, as well as tracking of CRISPR/Cas delivery, editing efficiency, and potential off-target effects. The development of CRISPR/Cas-loaded NPs allows for enhanced imaging and precise monitoring across multiple scales with multiplexed and multicolor imaging in complex settings, including potential <em>in vivo</em> diagnostics. CRISPR/Cas therapeutics as well as diagnostics are hindered by the lack of efficient and targeted delivery tools. Biomimetic NPs have emerged as promising tools for improving biocompatibility, enhancing targeting capabilities, and overcoming biological barriers, facilitating more efficient delivery and bioimaging of CRISPR/Cas systems <em>in vivo</em>. As the design of these NPs and delivery mechanisms improves, alongside advancements in endolysosomal escape, CRISPR/Cas-based bioimaging will continue to advance, offering unprecedented possibilities in precision medicine and theranostic applications.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115619"},"PeriodicalIF":15.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177293","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":"Polypharmacology approaches for brain disorders aimed to enhance brain permeability and circadian clock targeting","authors":"Dionysis Kampasis,&nbsp;Elisa Uliassi,&nbsp;Maria Laura Bolognesi","doi":"10.1016/j.addr.2025.115621","DOIUrl":"10.1016/j.addr.2025.115621","url":null,"abstract":"<div><div>Circadian rhythm disruption (CRD) is a common feature of several brain disorders. The restoration of circadian clock function and the development of circadian-based therapies may have significant therapeutic implications for brain diseases that extend beyond sleep disorders. However, several challenges persist due to the complexity of circadian interactions with multiple cellular pathways underlying CRD in brain diseases, together with the CNS compartmentalization, including the presence of the blood–brain barrier (BBB). Against these drawbacks, polypharmacology is a promising strategy to potentially provide greater efficacy by targeting multiple components of the CRD network through drug combinations or multi-target-directed ligands. Polypharmacology also offers innovative approaches to brain drug delivery by enhancing BBB penetration of CNS-directed drugs using combinations, co-drugs, and targeted prodrugs. Herein, we review polypharmacological strategies to improve BBB permeability of CNS agents and suggest the exploitation of polypharmacology as a promising new avenue for circadian clock modulation in the treatment of brain disorders.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"223 ","pages":"Article 115621"},"PeriodicalIF":15.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164848","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":"Corrigendum to “Light sheet fluorescence microscopy for monitoring drug delivery: unlocking the developmental phases of embryos” [Adv Drug Del. Rev. 218 (2025) 115520]","authors":"Gagan Raju ,&nbsp;Aymeric Le Gratiet ,&nbsp;Giuseppe Sancataldo ,&nbsp;Guan-Yu Zhuo ,&nbsp;Yury Kistenev ,&nbsp;Subir Das ,&nbsp;Ajeetkumar Patil ,&nbsp;Soubarno Kundu ,&nbsp;Tribikram Patel ,&nbsp;Nirmal Mazumder","doi":"10.1016/j.addr.2025.115609","DOIUrl":"10.1016/j.addr.2025.115609","url":null,"abstract":"","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"223 ","pages":"Article 115609"},"PeriodicalIF":15.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145723","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":"DNA-Based nanostructures for tumor microenvironment-responsive drug delivery","authors":"Siqi Li ,&nbsp;Mengdi Xu ,&nbsp;Chi Yao ,&nbsp;Dayong Yang","doi":"10.1016/j.addr.2025.115610","DOIUrl":"10.1016/j.addr.2025.115610","url":null,"abstract":"<div><div>DNA nanostructures, with sequence programmability, biocompatibility, and structural versatility, have emerged as promising tools for biomedical applications, particularly in targeted drug delivery and therapeutic interventions. The tumor microenvironment (TME) is characterized by dysregulated pH gradients, elevated glutathione (GSH), hypoxia, adenosine triphosphate (ATP) abundance, and aberrant enzymatic activity, presenting significant challenges for conventional therapies. DNA-based nanostructure enables precise control over drug-loading efficiency, tumor-targeted specificity, and spatiotemporal release mechanisms, making them ideal for tumor-targeted drug delivery. In this review, we highlight recent advances in versatile TME-responsive DNA-based nanostructures for precise therapeutic drug delivery. First, we discuss the fundamental design principles governing the structural configuration and functional integration of DNA nanostructures in TME-responsive drug delivery. Next, we summarize the mechanisms by which TME characteristics, including pH gradients, glutathione (GSH), adenosine triphosphate (ATP), enzymatic activity, and multiple stimuli, regulate the targeting and controlled release of therapeutic payloads in DNA-based nanostructures. Finally, this review provides an outlook on future research directions aimed at further optimizing the designability of DNA nanostructure-based drug delivery systems, underscoring the necessity of interdisciplinary collaboration. It is expected that these principles facilitate the future development of next-generation DNA nanostructure-based drugs with smart, precise, safe, and potent therapeutic capabilities.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"223 ","pages":"Article 115610"},"PeriodicalIF":15.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133647","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":"Maximizing therapeutic potential and safety: Exploring multi/dual-payload antibody conjugates as cancer theranostics","authors":"Meysam Khosravifarsani ,&nbsp;Fabrice Ngoh Njotu ,&nbsp;Dede Api Fon ,&nbsp;Humphrey Fonge","doi":"10.1016/j.addr.2025.115608","DOIUrl":"10.1016/j.addr.2025.115608","url":null,"abstract":"<div><div>Tumor heterogeneity greatly contributes to the failure of traditional cancer treatments. This leads to tumor relapse, recurrence, and ultimately metastasis, presenting serious clinical challenges. In recent decades, advances in antibody-based immunotherapy have emerged as promising new pillars to combat cancers. Although single payload antibody drug conjugates (ADCs) have resulted in drastic improvements in patient outcomes compared with unconjugated antibodies, multiple <em>de novo</em> and acquired resistance mechanisms inherent with cancer cells have left patients with less than desired outcomes. Newer studies are exploring the use of dual and multiple payload ADCs to enhance effectiveness. These payloads include chemotherapeutic and/or radiotherapeutic agents. The approaches leverage the synergistic effects of the different payloads alongside the immunotherapeutic properties of the antibody carriers. This review presents a comprehensive overview of dual-payload monoclonal antibody conjugates for cancer therapy and diagnosis (theranostics). Additionally, it explores the use of various imageable radiometals that are conjugated to the ADCs for imaging/diagnosis. It discusses the role of radioisotope decay schemes (such as alpha emission, beta emission, or Auger electron emission) along with factors such as linker type and chelator, as well as drug-to-antibody ratio (DAR), which are aimed at enhancing the synergistic effects between the therapeutic payloads while ensuring safety. Because none of these dual-payload ADCs have reached the clinic, this review employs a predictive method to estimate human equivalent dose (HED), maximum tolerable dose (MTD), and radiotoxicity in humans based on preclinical data. Additionally, it discusses the combinatorial behavior of two cytotoxic payloads linked to a monoclonal antibody.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115608"},"PeriodicalIF":15.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088034","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":"Nanomedicine for targeting brain Neurodegeneration: Critical barriers and circadian rhythm Considerations","authors":"Laura Pineiro-Alonso ,&nbsp;Inés Rubio-Prego ,&nbsp;Alexandra Lobyntseva ,&nbsp;Eva González-Freire ,&nbsp;Robert Langer ,&nbsp;María José Alonso","doi":"10.1016/j.addr.2025.115606","DOIUrl":"10.1016/j.addr.2025.115606","url":null,"abstract":"<div><div>The development of novel therapies for central nervous system (CNS) diseases, particularly neurodegenerative disorders like Alzheimer’s disease (AD), is a critical global health priority. Biotherapeutics, such as monoclonal antibodies (mAbs) and RNA-based therapies, have shown potential for treating brain disorders. However, their clinical progress is limited by their difficult access to their brain targets. At the preclinical level, nanotechnology has been shown, to help these molecules overcome the biological barriers that imped their adequate brain delivery. This review highlights advances in this area and the challenges for the translation to the clinic. Key nanotechnology-based strategies, such as surface modifications utilizing endogenous protein corona, functionalization with targeting ligands, therapeutic ultrasound-mediated microbubble oscillation were particularly analyzed. Additionally, in line with the focus of the Special Issue, this review integrates the concept of chronotherapy, with a focus on AD treatment, highlighting the idea that, by aligning nanoparticle (NP)-based drug delivery with circadian rhythms, it may be possible to improve therapeutic outcomes. Finally, the article analyzes current strategies in CNS drug delivery in clinical trials and provides future directions within this frame, notably in the area of AD.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115606"},"PeriodicalIF":15.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066511","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":"Enabling technologies for in situ biomanufacturing using probiotic yeast","authors":"William Parker ,&nbsp;Amanda Taylor ,&nbsp;Aryan Razdan ,&nbsp;Jose Escarce ,&nbsp;Nathan Crook","doi":"10.1016/j.addr.2025.115605","DOIUrl":"10.1016/j.addr.2025.115605","url":null,"abstract":"<div><div><em>Saccharomyces boulardii</em> (<em>Sb</em>) is a Generally Regarded As Safe (GRAS) probiotic yeast currently used to alleviate symptoms from various gastrointestinal diseases. <em>Sb</em> is a promising platform for probiotic and biotherapeutic engineering as it is the only probiotic eukaryote and carries with it a unique set of advantages compared to bacterial strains, including resistance to phage, high protein secretion abilities, and intrinsic resistance to antibiotics. While engineered <em>Sb</em> has not been studied as extensively as its close relative <em>Saccharomyces cerevisiae</em> (<em>Sc</em>), many genetic engineering tools developed for <em>Sc</em> have also shown promise in <em>Sb</em>. In this review, we address recent research to develop tools for genetic engineering, colonization modulation, biomarker sensing, and drug production in <em>Sb</em>. Ongoing efforts, especially those that overcome gut-specific challenges to engineered performance, are highlighted as they advance this chassis as a scalable platform for treating gastrointestinal diseases.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"223 ","pages":"Article 115605"},"PeriodicalIF":15.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067294","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":"Advances in enhancing photoprotection of sunscreens using hydrocarbon film formers and carbon nanomaterials","authors":"Ajoa J. Addae ,&nbsp;Jennifer Uyanga ,&nbsp;Joey Chifamba ,&nbsp;Paul S. Weiss","doi":"10.1016/j.addr.2025.115607","DOIUrl":"10.1016/j.addr.2025.115607","url":null,"abstract":"<div><div>Recent developments in sunscreen formulations have been made to enhance sunscreen films formed on the surface of the skin. Film formation is of particular interest for sunscreens because the ability of solubilized ultraviolet (UV) filters to adhere to the skin’s surface in such a way that they efficiently absorb UV light is a significant determinant of sun protection factor (SPF) value. Additionally, methods of stabilizing sunscreen films at the formulation level are of interest due to the degradation of sunscreen on skin-like substrates overtime. We note that traditional solvent-based spectroscopic methods of measuring sunscreens’ efficacy capture only a portion of the story when it comes to determining SPF value and photoprotective properties of sunscreens on human skin. In this forward-looking review, we highlight strategies for enhancing film formation in sunscreens using hydrocarbon film formers and carbon nanomaterials. We discuss challenges of maintaining adhesion of sunscreen films on skin-like substrates, outline properties of hydrocarbon film formers and carbon nanomaterials for improving photoprotection, and present best practices for analyzing sunscreen films at the formulation level. Overall, this review provides insights relevant for sunscreen formulators and clinicians who develop and evaluate sunscreen efficacy.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115607"},"PeriodicalIF":15.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945753","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":"Advances in photoactivated carbon-based nanostructured materials for targeted cancer therapy","authors":"Maryam Eftekharifar ,&nbsp;Reza Heidari ,&nbsp;Neda Mohaghegh ,&nbsp;Alireza Hassani Najafabadi ,&nbsp;Hossein Heidari","doi":"10.1016/j.addr.2025.115604","DOIUrl":"10.1016/j.addr.2025.115604","url":null,"abstract":"&lt;div&gt;&lt;div&gt;In this review, we explore key innovations in photoactivated therapeutic programming of carbon-based nanomaterials (CBNs), focusing on their diverse nanostructural configurations and their exceptional photothermal, photochemical, and photoacoustic properties. These attributes position CBNs as remarkable phototherapeutic agents, capable of addressing critical challenges in targeted cancer therapy through their precision, multifunctionality, and adaptability to specific therapeutic modalities. We will explore their diverse derivatives, and the role of chemical augmentation and site-specific surface functionalisation, which are pivotal in optimising the targeting and efficacy of phototherapeutic interventions. The biological and physical relevance of this ever-growing library of nanomaterials in targeted phototherapy will be thoroughly explored. Dynamic photo-triggering of the underlying molecular mechanisms of action e.g., energy conversion modalities lie at the heart of these therapeutic innovations. We will further discuss the tunability and programming of these carriers and structure–function alterations at specific therapeutic wavelengths. The application space of phototherapies is thoroughly mapped exploring the three primary approaches of photothermal therapy, photodynamic therapy and photochemical internalisation as well as emerging techniques and promising multimodal approaches that combine two or more of these processes. The specificity of the target tissue site and the approach under study forms another critical focus area of this review, with an emphasis on three types of cancer—breast cancer, lung cancer, and gliomas—that have demonstrated some of the most promising outcomes from photomedicine. We also provide a perspective on &lt;em&gt;in vitro&lt;/em&gt; and &lt;em&gt;in vivo&lt;/em&gt; validation and preclinical testing of CBNs for phototherapeutic applications. Finally, we reflect on the potential of CBNs to revolutionise targeted cancer therapy through data-driven materials design and integration with computational tools for biophysical performance optimisation. The exciting integration of machine learning into nanoparticle research and phototherapy has potential to fundamentally transform the landscape of nanomedicine. These techniques ranging from supervised learning algorithms such as random forests and support vector machines to more advanced neural networks and deep learning, can enable unprecedented precision in predicting, optimising, and tailoring the properties of nanoparticles for targeted applications. The transformative impact of photoactivated CBNs in advancing cancer treatment, paves the way for their clinical application and widespread adoption in personalised photomedicine. We conclude with a section on the current challenges facing the reproducibility, manufacturing throughput, and biocompatibility of these nanostructured materials including their long-term effects in trials and degradation profiles in biological systems as eval","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115604"},"PeriodicalIF":15.2,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932573","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":"Advanced microbiome therapeutics for oral delivery of peptides and proteins: Advances, challenges, and opportunities","authors":"Hitesh P. Gelli ,&nbsp;Ruben Vazquez-Uribe ,&nbsp;Stephen T. Buckley ,&nbsp;Jan Terje Andersen ,&nbsp;Morten Otto Alexander Sommer","doi":"10.1016/j.addr.2025.115603","DOIUrl":"10.1016/j.addr.2025.115603","url":null,"abstract":"<div><div>Peptide and protein medicines have changed the therapeutic landscape for many diseases, yet oral delivery remains a significant challenge due to enzymatic degradation, instability, and poor permeability in the gastrointestinal tract. Advanced Microbiome Therapeutics (AMTs) could overcome some of these barriers by producing and releasing therapeutic peptides directly in the gastrointestinal tract. AMTs can localize peptide production at the site of absorption, providing either sustained or controlled release while potentially reducing side effects associated with systemic administration. Here, this review assesses the status of AMTs for oral peptide delivery and discusses the potential integration of permeation enhancers, mucoadhesive systems, and receptor-mediated transport strategies to improve oral bioavailability further. Combining these approaches could pave the way for more widespread oral delivery strategies for peptide and protein medicines.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"222 ","pages":"Article 115603"},"PeriodicalIF":15.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927167","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}