{"title":"Genetically engineered M13 phage-mediated H9N2 DNA vaccine with enhanced mucosal and systemic immune responses in mice.","authors":"Xiaohua Wang, Zhi Zhao, Mingze Shi, Shangen Xu, Xin Zhou, Kai Zhao","doi":"10.1080/10717544.2026.2629037","DOIUrl":"10.1080/10717544.2026.2629037","url":null,"abstract":"<p><p>Vaccine adjuvants and delivery systems have long been used in DNA vaccines to enhance immunogenicity. In this study, we developed a DNA vaccine delivery platform by combining <i>N</i>-2-hydroxypropyl trimethyl ammonium chloride chitosan/carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with a genetically engineered M13 phage containing the HA gene of H9N2 AIV (HA-M13). The composite NPs (HA-M13/N-2-HACC/CMCS) had an average particle size of 135.24 ± 4.36 nm, and the HA gene encapsulated in the composite NPs could be expressed <i>in vitro</i>. Additionally, the N-2-HACC/CMCS NPs exhibited high stability and effectively protected the HA gene and M13 phage from degradation while sustaining antigen release. Furthermore, the N-2-HACC/CMCS NPs promoted the maturation of DC2.4, enhanced MHC I and MHC II pathways and improved cellular, humoral, and mucosal immune responses. Mice immunized with HA-M13/N-2-HACC/CMCS via nasal and intramuscular injections presented higher anti-H9N2 AIV antibody titers than those given the commercial vaccine. Lymphocyte proliferation, as well as the levels of the cytokines IL-2, IL-4, IFN-<i>γ</i>, CD4<sup>+</sup>, and CD8<sup>+</sup> T lymphocyte levels, also significantly increased. The nanovaccine provided effective protection against H9N2 AIV infection for 154 days postimmunization, surpassing the 120-day protection provided by the commercial vaccine. Consequently, the N-2-HACC/CMCS NPs loaded with M13 phages exhibit significant potential as vaccine adjuvants and mucosal immune delivery system.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2629037"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-01-03DOI: 10.1080/10717544.2025.2610532
Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen
{"title":"Long-term management of psoriasis recurrence via modulation of cutaneous microbiome: synergistic topical therapy with blue light and aptamer-functionalized curcumin formulation.","authors":"Nan Jin, Yaling Chen, Huangyu Luo, Yanhong Su, Yumin Weng, Xin Lin, Tingting Zheng, Bingbing Li, Tianhui Liu, Jianmin Chen","doi":"10.1080/10717544.2025.2610532","DOIUrl":"10.1080/10717544.2025.2610532","url":null,"abstract":"<p><p>The recurrence following the discontinuation of medication is a formidable challenge in managing psoriasis. Changes in the microbiome accompany the onset of psoriasis relapse, highlighting a potential therapeutic modality. To evaluate the superiority of the topical administration of aptamer-functionalized curcumin mesoporous silica (Apt-GA+Cur@μmS) plus blue light (BL) in restoring dysbiosis and intervening in recurrence in a murine model, a psoriasis relapse murine model with double imiquimod induction was established. With a BL-responsive shell, Apt-GA+Cur@μmS released curcumin (Cur) to assist BL to improve the preventative and therapeutic effects in the psoriasis relapse murine model, as evidenced by the psoriasis area and severity index, histology, splenic index, and dorsal IL-17A level. We also observed a negative correlation between splenic nitric oxide (NO) levels and the splenic index, indicating a possible mechanism by which Apt-GA+Cur@μmS&BL may function in the treatment of splenomegaly. Treatment with Apt-GA+Cur@μmS&BL exhibited a higher alpha diversity than the model group, with levels similar to those of healthy mice, indicating that this combination could adjust the composition of the dorsal microbiome to a healthier state. A reduction in the combined relative abundance of <i>Staphylococcus</i>, <i>Streptococcus,</i> and <i>Corynebacterium</i> as well as restoration of dysbiosis was also verified through 16S rDNA gene sequencing <i>in vivo</i>. Collectively, BL and Apt-GA+Cur@μmS cotherapy alleviates psoriasiform lesions in a double imiquimod-induced murine model by inhibiting IL-17A and increasing splenic NO. Additionally, this cotherapy restores the eubiosis of the dorsal lesions. Thus, it is a promising and innovative therapeutic modality for psoriasis inflammation alleviation and recurrence intervention.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2610532"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-01-06DOI: 10.1080/10717544.2025.2608235
Da Hee Oh, Ji Hee Kang, O Hyun Lee, Young Tag Ko
{"title":"Cell swelling and upright mounting-based imaging for high-resolution visualization of intracellular trafficking across the BBB using conventional confocal microscopy.","authors":"Da Hee Oh, Ji Hee Kang, O Hyun Lee, Young Tag Ko","doi":"10.1080/10717544.2025.2608235","DOIUrl":"10.1080/10717544.2025.2608235","url":null,"abstract":"<p><p>Receptor-mediated transcytosis (RMT) represents a promising strategy for delivering macromolecular and colloidal therapeutics across the blood-brain barrier (BBB). However, mechanistic elucidation of RMT remains limited by the difficulty of visualizing subcellular trafficking pathways. Conventional imaging approaches either lack sufficient spatial resolution or require costly, technically complex instrumentation. Here, we report a cell swelling and upright mounting-based (CSUM-based) imaging approach that reorients the Z-axis into the high-resolution XY-plane using standard confocal microscopy, enabling direct RMT visualization without computational reconstruction or specialized hardware. We tracked intracellular trafficking of transferrin (Tf) and anti-transferrin receptor antibody (anti-TfR Ab) as model cargos using our CSUM-based imaging approach via compartment-specific markers and time-resolved co-localization analysis. This approach resolved cargo-containing vesicles traversing from the apical to basolateral membranes. Tf completed transcytosis within 15 min, whereas anti-TfR Ab initially entered the endolysosomal pathway before rerouting to transcytosis under receptor saturation conditions. The CSUM approach provides a simple yet effective platform for high-resolution visualization of membrane transport and vesicle dynamics, offering broad applicability to drug delivery research and the design of brain-targeted therapeutics.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2608235"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-02-10DOI: 10.1080/10717544.2026.2627689
Yanfang Liu, Nan Luo, Xin Xi, Jinxia Hou, Xiaolu Li, Mingdeng Xia, Tao Yu, Yanyan Yang, Yong Liu
{"title":"Mitochondrial dysfunction and applications of mitochondrial-targeted delivery systems in atherosclerosis.","authors":"Yanfang Liu, Nan Luo, Xin Xi, Jinxia Hou, Xiaolu Li, Mingdeng Xia, Tao Yu, Yanyan Yang, Yong Liu","doi":"10.1080/10717544.2026.2627689","DOIUrl":"10.1080/10717544.2026.2627689","url":null,"abstract":"<p><p>Atherosclerosis, a chronic inflammatory disease, is pathologically associated with mitochondrial dysfunction. Mitochondria contribute to oxidative stress, vascular endothelial dysfunction, and chronic inflammatory cascades through pathways such as dynamic imbalance, abnormal epigenetic regulation, disruption of multi-organelle communication, and dysregulation of cell death signaling. Targeting mitochondria has therefore emerged as a promising therapeutic strategy beyond conventional treatments , which often fail to address this underlying pathology. Recent advances in nanomaterials enable precise mitochondrial intervention. Although conventional therapies such as statins and anti-inflammatory drugs can partially mitigate symptoms, they do not directly correct mitochondrial abnormalities and are often limited by systemic side effects. Recent progress in nanotechnology has enabled the development of mitochondria-targeted delivery systems, including liposomes, polymeric nanoparticles, and biomimetic carriers. These platforms enhance mitochondrial accumulation by incorporating targeting motifs or exploiting the negative mitochondrial membrane potential and specific interactions with outer membrane proteins. Among these, TPP⁺-modified liposomes can target the mitochondrial matrix via electrostatic interactions, effectively delivering drugs such as coenzyme Q10 to mitochondria, offering notable clinical potential. Moreover, Szeto-Schiller 31, which targets mitochondrial electron transport chain repair and reduces the secretion of inflammatory cytokines, has entered Phase II clinical trials. This review discusses the mechanistic role of mitochondrial dysfunction in atherosclerosis and evaluates the application of mitochondria-targeted delivery systems in atherosclerosis therapy. It also highlights the challenges these systems face, including issues related to delivery efficiency, biosafety, and targeting specificity. By linking molecular mechanisms with translational innovation, it highlights the significant potential of mitochondrial-targeted therapies.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2627689"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microalgae as novel drug-delivery system for biomedical field.","authors":"Yueyou Dai, Dandan Guo, Aifang Li, Wei Chen, Yi Yang, Shuxuan Li, Lianhe Yang, Shuying Feng","doi":"10.1080/10717544.2026.2616930","DOIUrl":"10.1080/10717544.2026.2616930","url":null,"abstract":"<p><p>Currently, increasing attention is being paid to the extraction and utilization of materials with special biological activities in nature or for medical applications. Owing to their unique biological characteristics and diverse application potential, microalgae are among the most promising materials in the field of biomedicine. Because of their diverse morphology and readily functionalizable surface, they can efficiently carry drugs and achieve targeted drug release. This can avoid major challenges of other methods related to toxicity, biocompatibility, and immunogenicity, which is important for the treatment of various diseases, particularly those related to hypoxia. Despite the distinct advantages of microalgae over other biomaterials, several challenges persist in their practical application. Herein, we comprehensively describe the current state of research on the microalgae drug-delivery system (MDDS). In particular, we explore various microalgae-based strategies and methods to improve the load capacity and stability of DDS, and to achieve target positioning and tracking. With further research on microalgae, their application prospects in DDSs will broaden. In the future, researchers will continue to explore the features and advantages of microalgae; develop more efficient, safe, and accurate DDSs; and provide more options for clinical treatments. Continued progress in microalgal cultivation technology and reduction in large-scale production costs will expand the clinical applications of MDDSs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2616930"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-01-22DOI: 10.1080/10717544.2026.2617688
Yongdeok Jo, Chaimae Gouya, William F Mieler, Jennifer J Kang-Mieler
{"title":"Advancements and challenges in ophthalmic microneedles to treat eye diseases.","authors":"Yongdeok Jo, Chaimae Gouya, William F Mieler, Jennifer J Kang-Mieler","doi":"10.1080/10717544.2026.2617688","DOIUrl":"10.1080/10717544.2026.2617688","url":null,"abstract":"<p><p>By 2050, more than 61 million people worldwide are expected to lose their vision due to conditions like age-related macular degeneration, glaucoma, diabetic retinopathy, and uveitis (Bourne et al. 2021). This anticipated rise highlights the urgent need for more effective treatment options. While progress continues in developing new pharmacological agents, treating ocular diseases with these therapies remains particularly challenging due to the eye's unique and complex anatomy. This is largely due to the limitations of current drug delivery methods, including systemic administration, topical delivery application, transscleral/periocular drug delivery, and intravitreal injections, which are associated with low bioavailability, side effects, and rapid drug clearance. Given these challenges, microneedles have emerged as a promising alternative. Their minimally invasive nature and ability to precisely target the anterior and posterior segments make them well suited for enhancing therapeutic outcomes while reducing systemic exposure and potential side effects, as well as improving patient adherence (Kang-Mieler et al. 2017; Gadziński et al. 2022). The purpose of this review is to discuss recent advancements, key challenges, and strategies for microneedle-based ocular drug delivery systems, with an emphasis on their potential to treat both anterior and posterior eye diseases.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2617688"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-01-15DOI: 10.1080/10717544.2026.2614585
Jagabandhu Bag, Subhankar Mukhopadhyay, Gouranga Nandi, Hein Min Tun
{"title":"Next-generation composite vesicular systems: an in-depth review of proniosomes in advanced drug delivery.","authors":"Jagabandhu Bag, Subhankar Mukhopadhyay, Gouranga Nandi, Hein Min Tun","doi":"10.1080/10717544.2026.2614585","DOIUrl":"10.1080/10717544.2026.2614585","url":null,"abstract":"<p><p>Proniosomes represent an advanced composite vesicular platform that integrates non-ionic surfactants, lipids, and biodegradable carriers to significantly improve drug solubility, stability, and transmembrane delivery. These dry powdery formulations are transformed into multiscale niosomes upon contact with a hydrated medium to achieve controlled release and enhanced drug permeability. This seminal review delineates the transformative potential of proniosomal systems in treating various diseases, detailing diverse routes of administration, formulation techniques, mechanisms of action, as well as their advantages and limitations. Proniosomes address major issues such as systemic toxicity, poor solubility, and erratic absorption while maintaining green chemistry principles owing to their biodegradable constituents. By critically analyzing the potential for industrial translation, this review highlights the knowledge gap on clinical studies, scalability, and regulatory issues. The translation potential has even been further enhanced by recent developments in bioconjugation and nanotechnology, such as ligand-anchored proniosomes that enable active targeting. The topic's relevance is evident, as proniosomes complement next-generation biotechnology tools, such as mRNA delivery, while offering a sustainable alternative to liposomes. By compiling the most recent data, this review strives to catalyze innovation in novel drug delivery, making it essential for researchers and pharmaceutical developers.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2614585"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.","authors":"Chenxi Feng, Rui Lou, Shipeng Chen, Furong Lin, Jiaqi Ge, Yuwen Zhang, Chaolong Lin, Chenghao Huang","doi":"10.1080/10717544.2026.2645769","DOIUrl":"10.1080/10717544.2026.2645769","url":null,"abstract":"<p><p>Antibody‒drug conjugates (ADCs) have taken on a significant role in precision oncology. These molecules, referred to as 'biological missiles', can deliver cytotoxic drugs directly to cancer cells. Traditional ADCs rely on endocytosis and intracellular release of payloads, but this approach becomes complicated due to issues like antigen loss, tumor heterogeneity, and impaired endocytosis, leading to therapeutic resistance. To address these challenges, noninternalizing ADCs have been developed, utilizing extracellular payload release methods. These structures employ advanced linker technologies to ensure stability in vivo and selective activation in the tumor microenvironment, achieving effective cytotoxic diffusion among tumor cells through the 'bystander effect'. This review discusses the evolution from early linker designs to complex methods based on tumor-specific conditions or external triggers. It also examines the categories of noninternalizing ADC linkers and the latest developments in clinical research, exploring prospects for enhancing the efficacy and safety of ADCs in oncology applications.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2645769"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-01-06DOI: 10.1080/10717544.2025.2610654
Chun-Yin Yang, Chih-Hua Tseng, Feng-Lin Yen
{"title":"Electrospun PVP/HPBCD nanofiber topical drug delivery platform for enhanced skin permeability and anti-pollution bioactivity of <i>Artocarpus altilis</i> extract.","authors":"Chun-Yin Yang, Chih-Hua Tseng, Feng-Lin Yen","doi":"10.1080/10717544.2025.2610654","DOIUrl":"10.1080/10717544.2025.2610654","url":null,"abstract":"<p><p><i>Artocarpus altilis</i> methanolic extract (AAM) exhibits potent protective effects against particulate matter (PM)-induced skin damage; however, its poor aqueous solubility and limited skin permeability restrict its topical bioavailability. To overcome these limitations, we developed a polymer-based drug delivery system by fabricating electrospun nanofibers composed of polyvinylpyrrolidone (PVP), hydroxypropyl-<i>β</i>-cyclodextrin (HPBCD), and AAM. The optimized formulation engineering strategy enhanced AAM solubility via increased surface area, reduced crystallinity, and hydrogen bonding interactions with HPBCD/PVP. The nanofiber matrix also provided an occlusive effect, improving skin hydration and facilitating transdermal diffusion through the stratum corneum. In vitro studies demonstrated improved cellular uptake, greater permeability, and enhanced antioxidant activity, leading to superior anti-pollution efficacy compared to raw AAM in a PM-induced HaCaT keratinocyte model. These results highlight AAM-loaded electrospun nanofibers (ANFs) as a biodegradable, and environmentally sustainable platform for delivering plant-derived bioactive ingredient, offering high potential for advanced topical formulations targeting pollution-induced skin aging.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2610654"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2026-12-31Epub Date: 2026-02-08DOI: 10.1080/10717544.2026.2626104
Haonan Li, Binghong Xu, Junguang Liang, Tao Hu, Tingting Wu, Liqin Lai, Xuan Zou, Ziquan Lv, Xiangjie Yao, Xiaobao Jin, Yinghua Xu, Shuiqing Gui, Xuemei Lu
{"title":"A macrophage-mimetic nanocarrier co-loaded with geraniol and FK13-a1 for MRSA-induced acute lung injury.","authors":"Haonan Li, Binghong Xu, Junguang Liang, Tao Hu, Tingting Wu, Liqin Lai, Xuan Zou, Ziquan Lv, Xiangjie Yao, Xiaobao Jin, Yinghua Xu, Shuiqing Gui, Xuemei Lu","doi":"10.1080/10717544.2026.2626104","DOIUrl":"10.1080/10717544.2026.2626104","url":null,"abstract":"<p><p>Current clinical strategies for Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-induced acute lung injury (ALI) predominantly focus on single-approach interventions such as anti-inflammatory therapy. However, due to the complex, multi-pathway pathological network underlying the disease, targeting a single pathway often yields suboptimal therapeutic outcomes. Consequently, there is a pressing need to develop innovative drug delivery systems capable of systematically addressing this intricate pathological process. Geraniol, a naturally derived monoterpene alcohol, exhibits multiple pharmacological activities including antimicrobial, antioxidant, and organ-protective effects, while the antimicrobial peptide (AMP) FK13-a1 demonstrates broad-spectrum antibacterial, anti-inflammatory, and immunomodulatory functions. Recognizing their complementary mechanisms of action, we innovatively propose a synergistic therapeutic strategy combining geraniol with FK13-a1. To enhance targeting precision, we engineered a biomimetic delivery system by coating nanomaterials with macrophage membranes via tyramine linkage, enabling specific homing to pulmonary inflammatory sites. Guided by this design concept, we successfully fabricated the biomimetic nanodrug Tyr-MM@PLGA/G+F and conducted systematic characterization using multiple analytical techniques. Through established <i>in vitro</i> and <i>in vivo</i> infection models, we evaluated the therapeutic efficacy of this nanosystem. Results demonstrated that Tyr-MM@PLGA/G+F actively targets ALI lesion sites, achieving precise co-delivery and synergistic action of geraniol and FK13-a1 at the pathological foci, thereby significantly enhancing treatment outcomes. This study not only validates the remarkable efficacy of this composite nanosystem against ALI but also provides novel insights and experimental evidence for targeted therapy of this condition.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"33 1","pages":"2626104"},"PeriodicalIF":8.1,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12888352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}