Drug Delivery and Translational Research最新文献

{"title":"Double-coated PLGA nanoparticles with hierarchical surface architecture for CD44-targeted siRNA delivery.","authors":"Giuseppe Longobardi, Pini Shekhter, Claudia Conte, Ronit Satchi-Fainaro, Fabiana Quaglia","doi":"10.1007/s13346-026-02115-8","DOIUrl":"https://doi.org/10.1007/s13346-026-02115-8","url":null,"abstract":"<p><p>Efficient delivery of small interfering RNA (siRNA) remains a materials challenge because it requires nanocarriers that stabilize polyanionic cargo, support cellular interactions, and enable cytosolic delivery. Although poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are used due to biocompatibility, biodegradability, and regulatory acceptance, siRNA delivery with PLGA requires interfacial engineering to meet these constraints. Here, a modular double-coated PLGA NP platform (dcNPs2.0) is developed and optimized for siRNA complexation, surface functionalization, and scalable manufacturing. The system comprises a PLGA core coated with a polyethyleneimine (PEI) interlayer to mediate siRNA binding, followed by a hyaluronic acid (HA) outer layer, which improves colloidal stability and promotes CD44-mediated uptake. Process optimization, including transition from batch nanoprecipitation to microfluidic fabrication, provides high yield, excellent reproducibility, narrow size distributions, and increased siRNA loading. X-ray photoelectron spectroscopy confirms hierarchical multilayer assembly. The optimized dcNPs2.0 formulation exhibited robust physicochemical stability during storage, in serum-containing media, and following lyophilization with appropriate cryoprotection. Functional evaluation of dcNPs2.0 demonstrated efficient HA-mediated cellular uptake and effective silencing following siRNA delivery in both two-dimensional monolayers and three-dimensional spheroids of MDA-MB-231 cells. Overall, this work establishes a scalable, rationally engineered PLGA nanoplatform that integrates extracellular targeting with intracellular delivery requirements for siRNA therapeutic applications.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal lipid nanocapsule administration of the new lipophenol quercetin-3-O-DHA-7-O-iPr reduces carbonyl stress and improves behavior in a mouse model of Alzheimer's disease.","authors":"Léa Otaegui, Jordan Lehoux, Sylvie Begu, Tristan Moujellil-Legagneur, Charleine Zussy, Mathieu Vitalis, Magalie Mathias, Annaëlle Beau, Thierry Durand, Laurent Givalois, Nathalie Bernoud-Hubac, Céline Crauste, Catherine Desrumaux","doi":"10.1007/s13346-026-02142-5","DOIUrl":"https://doi.org/10.1007/s13346-026-02142-5","url":null,"abstract":"<p><p>Oxidative and carbonyl stresses (COS), which damage brain cells through the accumulation of toxic reactive carbonyl species (RCS), are key players in the etiology of Alzheimer's disease (AD). Our group developed lipophenols, i.e. COS-targeting hybrid molecules combining polyunsaturated fatty acids (PUFAs) and alkyl-(poly)phenols. Among them, quercetin-3-O-docosahexaenoate-7-O-isopropyl (Quercetin-3-O-DHA-7-O-iPr or \"Q-iP-DHA\") afforded neuroprotection against acrolein-induced toxicity, reduced carbonyl stress, and lowered amyloid-beta secretion in neuroblastoma cells. To evaluate Q-iP-DHA in vivo, it was formulated into lipid nanocapsules (to allow solubilization) then administered intranasally to J20 transgenic mice, a model of AD. This approach was chosen to optimize blood-brain barrier (BBB) penetration. This delivery led to improvements in well-being, organizational skills and spatial memory. In addition, Q-iP-DHA treatment reduced hippocampal amyloid plaque numbers, normalized expression of the Receptor for Advanced Glycation End-products (RAGE), and decreased microglial activation, indicating anti-inflammatory effects. Overall, our preclinical findings suggest that intranasal administration of nanoformulated Q-iP-DHA may represent a promising multitarget therapeutic approach against AD.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A design of experiments study of nasal spray deposition in the alberta idealized nasal inlet.","authors":"Mathilde Sophie Felding, Charlotte Cubbin, Claus Moser, Fatemeh Ajalloueian, Line Hagner Nielsen","doi":"10.1007/s13346-026-02147-0","DOIUrl":"https://doi.org/10.1007/s13346-026-02147-0","url":null,"abstract":"<p><p>Intranasal administration of drugs possesses numerous advantages such as easy and direct application, rapid onset of action and reduced risk of systemic adverse effects. The nasal cavity consists of several regions and especially the respiratory region, known as the turbinates, is considered favorable for drug uptake. Current Food and Drug Administration (FDA) guidelines for in vitro testing of nasal spray formulations recommend characterization of emitted dose, plume geometry, spray pattern, and particle size distribution. However, recommendations or guidelines for assessing regional deposition within the nasal cavity remain lacking. In this study, we used the Alberta Idealized Nasal Inlet for in vitro testing and a design of experiments (DoE) approach to test the regional deposition of a commercially available nasal spray Otrivin^®. We show that three main parameters (airflow, angle of administration and temperature) play vital roles in the deposition pattern. Furthermore, we uncovered significant effects of administration angle and temperature, as well as combined interactions between airflow and angle, and temperature and airflow. Our results demonstrate the need for introducing a physiologically relevant temperature when conducting in vitro studies, and that combined interactions are vital to investigate and understand for assessing regional deposition of nasal spray formulations in vitro.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdermal ropivacaine delivery via hydrogel-forming microneedles: A pain-free alternative for local anaesthesia.","authors":"Andang Miatmoko, Qonita Kurnia Anjani, Rifda Tarimi Octavia, Natalia Porfiryeva, Febri Annuryanti, Gwan Young Kim, Ji Yeon Heo, Gwangheum Yoon, Ahreum Choi, Ryan F Donnelly","doi":"10.1007/s13346-026-02136-3","DOIUrl":"https://doi.org/10.1007/s13346-026-02136-3","url":null,"abstract":"<p><p>Surgical procedures in critical care settings are often associated with prolonged postoperative pain, which remains a significant clinical challenge. Conventional analgesic strategies typically rely on injection-based delivery, which is invasive, requires trained personnel, and carries risks such as infection and tissue damage. To address these limitations, this study developed a minimally invasive transdermal delivery system for the local anaesthetic ropivacaine (ROP) using hydrogel-forming microneedles (HFMNs) combined with drug reservoir tablets. Two HFMN formulations were prepared using Gantrez^® S-97 (MN1) and PVA-PVP (MN2), each paired with reservoirs fabricated by direct compression (DCT) or lyophilisation (LYO). Insertion capability study demonstrated that MN2 exhibited superior skin penetration compared with MN1. In vitro permeation studies showed that MN2-DCT achieved the highest transdermal delivery of ROP (> 12 mg across dermatomed porcine skin). However, when both permeated and deposited drug (within skin and HFMNs) were considered, LYO reservoirs paired with either MN1 or MN2 resulted in higher total drug delivery over 24 h. This is attributed to the porous structure of LYO tablets, which enhances fluid uptake and rapid dissolution. The retained drug within the skin and HFMN matrix may serve as a depot for sustained release. In vivo evaluation in a postoperative pain mouse model demonstrated that MN2-LYO provided rapid and sustained analgesia, achieving > 50% maximum possible effect (%MPE) within 1 h and maintaining efficacy for up to 72 h, whereas MN1-LYO showed limited analgesic response. Furthermore, both MN1-LYO and MN2-LYO significantly reduced inflammatory cytokines (IL-6 and TNF-α), with the greatest reduction observed for MN2-LYO (~ 50% decrease compared with negative control and subcutaneous ROP groups). Overall, these findings highlight the potential of HFMN-based delivery systems combined with LYO reservoirs as a minimally invasive, patient-friendly alternative to injectable anaesthetics for prolonged postoperative pain management.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual role of ascorbyl Palmitate as coagel and adjuvant in experimental antivenom development.","authors":"Franco M Maslovski, Sofía G Brignone, Bruno Barrientos, David R Hernández, María Del Rosario Alonso, Gisela L Lopez, Gonzalo A Ojeda, Felicitas Peyrano, Ana M González, Santiago D Palma, Laura C Leiva, Maletto Belkys, Luciano S Fusco","doi":"10.1007/s13346-026-02137-2","DOIUrl":"https://doi.org/10.1007/s13346-026-02137-2","url":null,"abstract":"<p><p>An ideal vaccine adjuvant should be biocompatible, enable antigen storage and controlled release, and effectively stimulate the immune system. In this study, we evaluated the dual functionality of ascorbyl palmitate (ASC16): as an adjuvant additive in its dispersed state (120 µM), and as a coagel formed at low temperatures and high ASC16 concentrations (Coa-ASC16_PEG), for use in the antivenom development. Coa-ASC16_PEG was prepared by mixing ASC16 with polyethylene glycol 400 (PEG400) and solubilising the mixture at 64 °C for 2 min; subsequently, the formulation was allowed to cool to 40 °C and whole Crotalus durissus terrificus venom, which naturally contains a complex mixture of proteins, was incorporated for 10 s, including major toxins such as crotoxin, serine proteinases, L-amino acid oxidase, and phosphodiesterases. To produce experimental antivenom, mice were immunized with Coa-ASC16_PEG or Freund's adjuvant, with or without the addition of dispersed ASC16. The physicochemical analyses showed that the Coa-ASC16_PEG exhibited a semi-crystalline, viscoelastic structure capable of effectively encapsulating and releasing proteins. The addition of dispersed ASC16 enhanced the immune response induced by both adjuvants (Freund's and Coa-ASC16_PEG), yielding up to a 1.2-fold increase in venom-specific IgG titres and an approximately 2.7-fold increase in IgG antibody avidity. ASC16-based formulations were associated with reduced local adverse reactions compared with Freund's adjuvant-based formulations. In conclusion, we propose an alternative ASC16-based formulation obtained at low temperatures that preserves key physicochemical properties and shows minimal impact at the inoculation site. Moreover, the incorporation of dispersed ASC16 as an additive enhances the humoral immune response. Taken together, our results obtained in a murine model position ASC16 as a promising adjuvant, demonstrating reduced local reactogenicity compared with Freund's adjuvant.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.","authors":"Farshid Jaberi Ansari, Javad Behroozi, Mohsen Chamanara, Mostafa Shahrezaee, Ali Shakerimoghaddam, Seyed Hossein Mousavi, Amir Amanzadeh, Mohammad Ali Shokrgozar, Hossein Ahmadi Tafti, Mahdi Ghorbani, David W Greening, Reza Heidari","doi":"10.1007/s13346-026-02143-4","DOIUrl":"https://doi.org/10.1007/s13346-026-02143-4","url":null,"abstract":"<p><p>Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free nanocarriers capable of targeted delivery and intercellular communication. Leveraging these advantages, engineered EVs were investigated in this study as a direct ATP-delivery platform to cardiomyocytes. EVs were functionalized with an anti-myosin antibody to form targeted extracellular vesicles (T-EVs) and subsequently loaded with ATP, generating T-ATP-EVs for selective energy transfer to damaged myocardium. We study viability and apoptosis of ischemia cells by alamar Blue and flowcytometry (annexin-PI) under hypoxic condition in vitro also we use cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI on MI rat model in vivo for assessment cardiac repair. The results indicate that, compared with no treatment, the use of T-ATP-EVs enhances the viability of hypoxic cells by 46% and reduces apoptosis by 40%. In the animal study, T-ATP-EVs group increase 27% left ventricular ejection fraction (LVEF) also infarct size decrese 28% compared with control group. Additionally, the expression levels of troponin and α-actin increased approximately two-fold when we use T-ATP-EVs in vivo. In this study, T-ATP-EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue . The system described here enhances cardiomyocyte survival and targeting damaged heart tissue which making a significant advancement in the treatment of MI.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing insulin for Alzheimer's disease treatment: intranasal delivery of a thermoresponsive nanocarrier-based insulin formulation to the brain.","authors":"Tanisha Tabassum Sayka Khan, Chun Yuen Jerry Wong, Zara Sheikh, Ali Fathi, Simin Maleknia, Farshad Oveissi, Terence Abrams, Will Knox, Julia van der Hoven, Abi Antonito, Michael Murray, Maree Svolos, Julie Suman, Ole Tietz, Hui Xin Ong, Daniela Traini","doi":"10.1007/s13346-026-02146-1","DOIUrl":"https://doi.org/10.1007/s13346-026-02146-1","url":null,"abstract":"<p><p>The Intranasal route provides an effective pathway for insulin delivery to the brain compared to oral/subcutaneous routes as it provides direct access to the brain, bypassing the restrictive blood-brain barrier (BBB), while minimizing systemic exposure. The present study investigated the potential of a thermoresponsive polymer, PNPHO, as a nanocarrier for brain-targeted insulin delivery through the intranasal route, with the aim of repurposing insulin for Alzheimer's disease treatment. Insulin-loaded nanoparticles (NP) were formulated using an advanced crossflow mixing technology with lower (F1) and higher (F2) PNPHO concentrations and characterised in vitro for size, zeta potential, encapsulation efficiencies, stability, drug deposition, and transport and in vivo for biodistribution. Both F1 and F2 NP demonstrated particle sizes ranging from 35.9 to 49.8 nm with low polydispersity index (< 0.3), negative surface charges, high encapsulation efficiencies (> 99%), and conserved structural integrity post 4 weeks of stability study. NP demonstrated significantly greater in vitro nasal deposition compared to insulin alone. Notably, the PNPHO nanocarrier protected insulin from enzymatic degradation, overcoming a key barrier associated with protein/peptide delivery. In vitro drug transport studies showed an initial delay in NP transport across nasal cells due to PNPHO-mucoadhesive properties, followed by increased transport. Significantly enhanced time-dependent NP transport across the BBB cells compared to insulin alone (p < 0.0001) confirmed NP's ability to cross the BBB. In vivo, NP demonstrated prolonged nasal retention and higher brain: serum ratio in mice, suggesting sustained drug release and improved brain delivery compared to insulin alone. Collectively, the study highlight the potential of PNPHO as a promising nanocarrier for achieving targeted and efficient intranasal delivery of insulin to the brain.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellulose and its potential applications in skin biology; a comprehensive review.","authors":"Aasia Hameed, Adnan Haider, Hussain Mustatab Wahedi","doi":"10.1007/s13346-026-02140-7","DOIUrl":"https://doi.org/10.1007/s13346-026-02140-7","url":null,"abstract":"<p><p>Cellulose is the most abundant natural biopolymer obtained from plants, animals, and microbes. Cellulose is porous, biocompatible, biodegradable, noncytotoxic, and can retain water for a longer period. Therefore, cellulose has various applications in the medical, cosmetic, paper, and food industries. The current review summarizes the recent progress related to the application of cellulose in skin biology. Cellulose is preferable for skin biology applications due to its porosity, and hygroscopic nature that enables it to mimic the extracellular matrix (ECM) of native skin. Cellulose can be modified by combining with other biopolymers to make a functional cellulose composite. Researchers have developed various cellulose composites that are successfully used as wound dressing agents, scaffolds for skin tissue engineering, and vehicles for drug delivery like anticancer or other hydrophobic drugs. Cellulose-based facial masks act as a carrier for active agents like anti-aging, anti-wrinkle, and anti-acne substances. Cellulose can also be used as a stabilizer in the preparation of emulsion-based creams and other cosmetic products. It is concluded that cellulose is a suitable biopolymer in the global marketplace for skin applications, but further advancements should be made to maximize its clinical use.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tabletting of single-screw hot melt extruded itraconazole: HPMC-AS amorphous solid dispersion by 3D printing and direct compression.","authors":"Rachel L Milliken, Thomas Quinten, Sune K Andersen, Dimitrios A Lamprou","doi":"10.1007/s13346-026-02134-5","DOIUrl":"https://doi.org/10.1007/s13346-026-02134-5","url":null,"abstract":"<p><p>This study investigated the development of high drug loading amorphous solid dispersions (ASDs) of itraconazole (ITZ) using single screw hot melt extrusion (HME) for fused deposition modelling (FDM) 3D printing (3DP). ITZ ASDs containing 20-22% w/w ITZ were prepared with Hydroxypropyl methylcellulose acetate succinate, medium grade, medium particle (HPMCAS-MMP) and processed into filaments for 3DP, while a conventional direct compression ASD was produced as a benchmark to assess the influence of manufacturing method on drug release. While both dosage forms were based on the same ASD system, the final tablet compositions differed due to the requirements of each manufacturing method. Solid-state characterisation using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) confirmed the amorphous nature of the formulations. Dissolution studies were conducted in phosphate buffer saline (PBS, pH 7.4). The direct compressed ASD tablets showed rapid drug release (~ 63% in 30 min) while much slower release was observed for the 3D printed tablets. At 30 min F1 (10% triethyl citrate (TEC)) released only 3% and F2 (12.5% TEC) released 6%. This behaviour may be attributed to the printed tablet's dense structure, buoyancy, and formation of a viscous hydrogel barrier at the surface. This study shows that single screw HME can be used to produce ITZ ASDs for both 3DP and conventional tabletting, while also demonstrating that the dense microstructure of 3D printed tablets limits their ability to achieve an immediate release profile. Further optimisation of formulation and tablet design, such as infill will be needed to improve release performance. These findings provide a basis for future formulation and design strategies to enhance the performance of 3D printed dosage forms.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploitation of cholesterol-dependent cytolysins for targeted biosensing and therapeutic systems.","authors":"Henry O Abanum, Ethan Watt, Emmanuel A Ho","doi":"10.1007/s13346-026-02128-3","DOIUrl":"https://doi.org/10.1007/s13346-026-02128-3","url":null,"abstract":"<p><p>Cholesterol-dependent cytolysins (CDCs) represent a unique and structurally conserved family of pore-forming toxins secreted by Gram-positive bacterial pathogens. These exotoxins significantly contribute to the virulence and pathogenicity of many CDC-expressing organisms. CDCs selectively recognize and bind cholesterol-rich membranes in host cells and undergo subsequent conformational changes leading to pore formation. Beyond their role as virulence factors, their unique membrane-targeting and pore-forming mechanisms have enabled promising avenues in precision biosensing and targeted therapeutic delivery. Recent advances in nanotechnology and biotechnology have enabled diverse and pivotal biomedical applications of CDCs, which encompass their exploitation as potential bacterial vaccine candidates, ligands for targeted drug delivery, biosensors for pathogen detection, and CDC-responsive nanocarriers for targeted therapeutic delivery. This review explores these emerging roles while highlighting critical factors for the design and evaluation of CDC-responsive platforms, as well as strategies for characterizing their interactions with biological systems. While several preclinical models have demonstrated promising in vitro and in vivo data, the clinical translation of CDC-associated therapies remains hindered by challenges which affect their widespread biomedical application. Understanding the biological mechanisms and molecular interactions of CDCs, along with the effective optimization of the physicochemical properties of CDC-targeted nanomaterials, holds great prospect in overcoming these challenges. Future research focusing on enhanced understanding of CDC physiological interactions and developing innovative CDC-responsive nanoplatforms for targeted delivery offers valuable prospects in advancing this field and may ultimately enable the successful clinical translation of CDC-based therapies. Despite current challenges in ongoing research, the strategic exploitation of CDCs holds significant potential in the advancement of targeted biosensing and therapeutic innovations.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}