Advanced drug delivery reviews最新文献

{"title":"Harnessing epigenetic inhibitors: A promising approach for overcoming challenges in pancreatic ductal adenocarcinoma treatment","authors":"Immacolata Maietta ,&nbsp;África González-Fernández ,&nbsp;Rosana Simón-Vázquez","doi":"10.1016/j.addr.2025.115638","DOIUrl":"10.1016/j.addr.2025.115638","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and often fatal form of malignancy frequently diagnosed at an advanced stage, posing significant challenges for treatment. The complex and intricate microenvironment of PDAC, characterized by heterogenous tumoral cells harbouring diverse mutations and epigenetic alterations, immune cells (primarily in an immunosuppressive state), cancer-associated fibroblasts (CAFs), low vascularization and extracellular matrix components supporting tumor growth, creates a physical barrier that impedes drug delivery and anti-tumoral immune cell responses, leading to therapy resistance. Despite advancements in early detection methods, and available treatments for PDAC—including surgery, radiotherapy, chemotherapy, and immunotherapy, all have shown limited efficacy. Recently, liposomal drugs in combination therapy, PDAC-targeted CAR-T cells and anti-tumor RNA vaccines have emerged as promising therapeutic approaches. However, significant challenges remain, including the presence of a dense stroma, resistance to chemotherapy, and robust immune suppression, all of which pose substantial barriers to effective treatments.</div><div>In this context, epigenetic therapy aims to modify gene expression patterns in PDAC cells, potentially curtailing their resistance. This review provides an overview of the current landscape of PDAC research and the role of epigenetic inhibitors in the treatment of this lethal disease, emphasizing the potential of combining these novel drugs with conventional chemotherapy or immunotherapy, new drug delivery approaches and future directions in the field. A multi-approach therapy, switch to simultaneously targeting various facets of the PDAC characteristics, could enhance the anti-tumoral efficacy by overcoming its resistance mechanisms, improving patient prognosis.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115638"},"PeriodicalIF":15.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293151","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":"A new era in brain drug delivery: Integrating multivalency and computational optimisation for blood–brain barrier permeation","authors":"Giulia Porro ,&nbsp;Marco Basile ,&nbsp;Zhengdong Xie ,&nbsp;Gian Marco Tuveri ,&nbsp;Giuseppe Battaglia ,&nbsp;Cátia D.F. Lopes","doi":"10.1016/j.addr.2025.115637","DOIUrl":"10.1016/j.addr.2025.115637","url":null,"abstract":"<div><div>Efficient drug delivery across the blood–brain barrier (BBB) remains a significant obstacle in treating central nervous system (CNS) disorders. This review provides an in-depth analysis of the structural and molecular mechanisms underlying BBB integrity and its functional properties. We detail the role of key cellular and molecular components that regulate selective molecular transport across the barrier, alongside a description of the current therapeutic approaches for brain drug delivery, including those leveraging receptor-mediated transcytosis. Emphasis is placed on multivalency-based strategies that enhance the specificity of nanoparticle targeting and improve transport efficacy across the BBB. Additionally, we discuss the added value of integrating mathematical and computational models with experimental validation for accelerating BBB-targeted delivery systems optimisation.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115637"},"PeriodicalIF":15.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288633","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":"Aptamer-based applications in delivering cancer gene therapies and beyond: state of the art and the missing links to clinical translation","authors":"Gabriele Coppola ,&nbsp;Fabiola Cennamo ,&nbsp;Giuseppe Ciccone ,&nbsp;Maria Luigia Ibba ,&nbsp;Annalisa Di Ruscio ,&nbsp;Aldo Di Vito ,&nbsp;Carla Lucia Esposito ,&nbsp;Silvia Catuogno","doi":"10.1016/j.addr.2025.115639","DOIUrl":"10.1016/j.addr.2025.115639","url":null,"abstract":"<div><div>The possibility of correcting genetic and epigenetic alterations through gene therapies has been considered a cornerstone in oncology. However, modest results have been achieved in clinics, mainly due to inefficient tumor targeting and side effects. Nucleic acid aptamers are three-dimensional folded single-stranded DNAs or RNAs that selectively bind receptors on cellular membranes, being subsequently internalized via receptor-mediated endocytosis. Thanks to this capability, internalizing aptamers have been investigated as targeting moieties to deliver gene therapies more efficiently and selectively in tumor cells. Promising preclinical results suggested that aptamers could represent the long-awaited step forward in cancer gene therapy. Nevertheless, no clinical trials of aptamer-based gene therapies have been carried out two decades after the first preclinical application, indicating the field could not be sufficiently mature for translatability.</div><div>The review aims to update the<!--> <!-->state of the art regarding aptamers’ contribution to gene therapy delivery and to critically highlight the main shortcomings that could have hindered clinical evaluations. In addition, pioneering insights regarding the use of aptamers as co-factors in CRISPR/Cas9 technology or as direct epigenetic regulators are also summarized, revealing more extended applicability not limited to the delivery of cancer gene therapies.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115639"},"PeriodicalIF":15.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269250","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":"3D printed metamaterials: properties, fabrication, and drug delivery applications","authors":"Hemant Singh ,&nbsp;Muath Tuffaha ,&nbsp;Shivi Tripathi ,&nbsp;Ayça Bal Öztürk ,&nbsp;Harshil Dave ,&nbsp;Mukesh Dhanka ,&nbsp;Huseyin Avci ,&nbsp;Himansu Sekhar Nanda ,&nbsp;Shabir Hassan","doi":"10.1016/j.addr.2025.115636","DOIUrl":"10.1016/j.addr.2025.115636","url":null,"abstract":"<div><div>Drug delivery is a process to deliver the required amount of a drug to a target site within an appropriate timeframe, while minimizing possible side effects and maximizing efficiency. This is accomplished by drug delivery systems (DDSs), which are platforms composed of natural and/or synthetic materials that carry drugs or bioactive agents at a particular site or throughout a patient's body via oral, transdermal, topical, intravenous, or intramuscular routes to minimize the drug’s toxicity and provide desired therapeutic effects without affecting the patient’s healthy cells, tissues or organs. Despite significant advancements, drug delivery still faces numerous scientific, technological, and clinical challenges, such as poor drug bioavailability, unstable loading efficiency, lack of site-specificity, undesired prolonged delivery of drugs. Issues such as drug stability, limitations in achieving controlled and sustained release, long-term unwanted toxicity, and patient compliance are also common challenges in the field. In recent years, researchers have created 'Metamaterials', which exploit the advancements in fabrication and 3D printing technology to exhibit complex characteristics and customizable architecture that are not otherwise naturally present in a material. These properties provide a precision control over drug release kinetics, targeting, and efficiency by precise manipulation of interactions at the nanoscale. This review explores the potential of metamaterials in developing advanced DDSs with exceptional precision and efficacy, via materials selection, design considerations, fabrication challenges, and optimization strategies for 3D printing of these materials. We provide an overview of their recent application in drug delivery tackling the challenges associated with release systems, including sustained, pulsatile, and on-demand delivery modalities. Targeted delivery, theranostic applications, and regenerative medicine, are also explored. We believe this review will inspire further research and development in this burgeoning field by highlighting the challenges associated with their biocompatibility, scalability, manufacturing considerations, and hurdles or opportunities in translation, ultimately leading to transformative advancements in personalized medicine and healthcare.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115636"},"PeriodicalIF":15.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252534","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":"Smart drug delivery platforms reprogramming cancer immune cycle to mitigate immune resistance of pancreatic tumors","authors":"Ping Zhang ,&nbsp;Jiaxing Pan ,&nbsp;Shutong Lin ,&nbsp;Bo Peng ,&nbsp;Caiyan An ,&nbsp;Junjing Zhang ,&nbsp;Leiming Xu ,&nbsp;Yi Lai ,&nbsp;Haijun Yu ,&nbsp;Zhiai Xu","doi":"10.1016/j.addr.2025.115620","DOIUrl":"10.1016/j.addr.2025.115620","url":null,"abstract":"<div><div>Immunotherapy has emerged as a promising strategy for pancreatic ductal adenocarcinoma (PDAC) therapy, yet its clinical efficacy suffers from the immunosuppressive tumor microenvironment (ITM). This ITM contributes to immune resistance by impeding the cancer immune (CI) cycle at multiple stages, including impaired antigen release and presentation, inadequate T cell priming and activation, restricted T cell infiltration, and compromised T cell cytotoxicity within the tumor. To address these challenges, smart drug delivery systems have emerged as a transformative strategy to precisely modulate the CI cycle, thereby reversing the ITM and restoring the anti-tumor immunity. In this review, we systematically dissect the clinical landscape of PDAC immunotherapy, outline key mechanisms of impaired CI cycle to drive immunotherapy resistance, and explore smart drug delivery platforms for reinitiating CI cycle. We further discuss the latest preclinical advances of precisely engineered drug delivery systems, and provide a perspective on their potential to harness the CI cycle and overcome immunotherapy resistance in PDAC. This review not only summarizes current progress but also provides a forward-looking perspective on next-generation immunotherapies, emphasizing the role of neuro-immune interactions and the rational design of spatiotemporally tunable, circadian rhythm-adaptable drug delivery systems.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":"224 ","pages":"Article 115620"},"PeriodicalIF":15.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176961","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":"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}