Drug Delivery最新文献_第2页

Orchestrating T and NK cells for tumor immunotherapy via NKG2A-targeted delivery of a de novo designed IL-2Rβγ agonist. 通过nkg2a靶向递送一种全新设计的IL-2Rβγ激动剂，协调T和NK细胞用于肿瘤免疫治疗。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-04-01 DOI: 10.1080/10717544.2025.2482195

Jie Chen, Enhui Ren, Ze Tao, Hongyu Lu, Yunchuan Huang, Jing Li, Yuzhe Chen, Zhuo Chen, Tianshan She, Hao Yang, Hong Zhu, Xiaofeng Lu

{"title":"Orchestrating T and NK cells for tumor immunotherapy via NKG2A-targeted delivery of a de novo designed IL-2Rβγ agonist.","authors":"Jie Chen, Enhui Ren, Ze Tao, Hongyu Lu, Yunchuan Huang, Jing Li, Yuzhe Chen, Zhuo Chen, Tianshan She, Hao Yang, Hong Zhu, Xiaofeng Lu","doi":"10.1080/10717544.2025.2482195","DOIUrl":"10.1080/10717544.2025.2482195","url":null,"abstract":"As T and NK cell exhaustion is attributed to increased expression of immune checkpoints and decreased production of proliferative cytokines by these cells, immune checkpoint-targeted delivery of proliferative cytokines might induce robust and sustained antitumor immune responses. Here, the expression profile of NKG2A was first found to be narrower than that of PD-1 in tumor-infiltrated immune cells. Moreover, unlike PD-1, NKG2A was predominantly co-expressed with IL-2Rβγ in tumor-infiltrated CD8+ T and NK cells, but not in Tregs, suggesting that NKG2A might be an ideal target for delivery of IL-2Rβγ agonists to overcome T and NK exhausting. For NKG2A-targeted delivery of an IL-2Rβγ agonist, a single molecule of de novo designed N215 endowed with Immunoglobin G(IgG)-binding ability was coupled to an antibody against NKG2A (αNKG2A) to produce αNKG2A-N215. NKG2A- and IL-2Rβγ-binding were well preserved in αNKG2A-N215, allowing αNKG2A-N215 to act as both an immune checkpoint inhibitor and a T and NK cell stimulator. Intravenously injected αNKG2A-N215 predominantly induced expansion of tumor-infiltrated CD8+ T and NK cells while showing little stimulation of Tregs. Compared with the separate combination using αNKG2A and N215, αNKG2A-N215 exerted a greater antitumor effect in mice bearing MC38 or B16/F1 tumors. 50% of mice bearing MC38 tumors were cured by αNKG2A-N215, and long-term immunological memory against the tumor was induced in these mice. These results indicate that NKG2A is another ideal target for delivery of an IL-2Rβγ agonist, and αNKG2A-N215, with specificities for both NKG2A and IL-2Rβγ, might be developed as a novel agent for immunotherapy.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2482195"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763232","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}

引用次数: 0

Application of chitosan-based drug delivery systems in the treatment of bacterial diseases: a review. 壳聚糖基给药系统在细菌性疾病治疗中的应用综述。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-06-10 DOI: 10.1080/10717544.2025.2514140

Huan Huang, Yaxin Zhou, Jiehang Li, Zhijin Zhang, RongJia Han, Jingru Zuo, Yubin Bai, Jiyu Zhang

{"title":"Application of chitosan-based drug delivery systems in the treatment of bacterial diseases: a review.","authors":"Huan Huang, Yaxin Zhou, Jiehang Li, Zhijin Zhang, RongJia Han, Jingru Zuo, Yubin Bai, Jiyu Zhang","doi":"10.1080/10717544.2025.2514140","DOIUrl":"10.1080/10717544.2025.2514140","url":null,"abstract":"Bacterial diseases are a significant challenge to human and animal health. The current treatment methods still have obvious shortcomings, such as poor targeting, low bioavailability, high side effects and drug resistance. Chitosan, with its outstanding biocompatibility, biodegradability, adhesiveness, antimicrobial properties, and ability to minimize drug side effects while improving bioavailability and therapeutic outcomes, serves as an ideal material for drug delivery systems, presenting a promising strategy for treating bacterial diseases. In this review, we briefly summarize the preparation methods of chitosan-based drug delivery systems and their application in the treatment of bacterial infections. The advantages of preparation of different types of chitosan-based drug delivery systems are discussed, supported by examples demonstrating their ability to improve drug antimicrobial activity, targeting, and bioavailability. Moreover, the current challenges, limitations, and future perspectives in this field were discussed, laying the groundwork for further development of chitosan-based drug delivery systems as high-performance and safe antimicrobial therapeutics.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2514140"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257600","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}

引用次数: 0

Ionic liquid-iontophoresis mediates transdermal delivery of sparingly soluble drugs. 离子液体-离子透入介导少溶性药物的透皮递送。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-04-21 DOI: 10.1080/10717544.2025.2489730

Wenyan Gao, Wenmin Xing, Zhan Tang, Qiao Wang, Wenying Yu, Qi Zhang

{"title":"Ionic liquid-iontophoresis mediates transdermal delivery of sparingly soluble drugs.","authors":"Wenyan Gao, Wenmin Xing, Zhan Tang, Qiao Wang, Wenying Yu, Qi Zhang","doi":"10.1080/10717544.2025.2489730","DOIUrl":"https://doi.org/10.1080/10717544.2025.2489730","url":null,"abstract":"Low solubility restricted transdermal penetration of drugs. We aimed to develop a novel ionic liquid-iontophoresis (IL-IS) technology and assess their efficacy and primary factors in facilitating transdermal drug delivery. Five choline-based ILs with different chain length were synthesized and validated, and the impact of IL and/or IS technology on transdermal penetration of model drugs were investigated. The results indicated that five groups of ILs synthesized in this study exhibited minimal level of toxicity, and the longer the chain of acid ligands of ILs, the greater the cytotoxicity. The longer chain of acid ligand was demonstrated superior solubilizing capabilities compared to the shorter chain. Cinnamic acid-choline-based IL ([Cho] [Cin]) significantly improved permeation of all three model drugs, and permeation quantity was linearly positively associated with the concentration of ILs. The 10 h cumulative permeation of aripiprazole applied with ILs alone was enhanced by about 14-fold when paired with IS, and the penetration was linearly positively associated with the concentration and current strength of the ILs. In vivo results indicated that IL and/or IS technology primarily facilitated drug penetration into the skin, with potential involvement of endocytosis in this process. This study demonstrated that [Cho] [Cin] exhibited a significant enhancement in the transdermal delivery of three sparingly soluble drugs. It further enhanced the transdermal permeation of weak base drug following with the combining IL and IS technology. These findings highlighted that the IL-IS technology holded promise for facilitating the transdermal delivery of sparingly soluble and weak base drugs.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2489730"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997039","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}

引用次数: 0

Selective expansion and differentiation of antigen-specific CD4⁺ T-helper cells by engineered extracellular vesicles. 通过工程细胞外囊泡对抗原特异性CD4+ t辅助细胞的选择性扩增和分化。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-06-12 DOI: 10.1080/10717544.2025.2509969

Ryouken Kimura, Tomoyoshi Yamano, Uryo Onishi, Xiabing Lyu, Kanto Nagamori, Toan Van Le, Mitsutoshi Nakada, Rikinari Hanayama

{"title":"Selective expansion and differentiation of antigen-specific CD4+ T-helper cells by engineered extracellular vesicles.","authors":"Ryouken Kimura, Tomoyoshi Yamano, Uryo Onishi, Xiabing Lyu, Kanto Nagamori, Toan Van Le, Mitsutoshi Nakada, Rikinari Hanayama","doi":"10.1080/10717544.2025.2509969","DOIUrl":"https://doi.org/10.1080/10717544.2025.2509969","url":null,"abstract":"Extracellular vesicles (EVs), particularly small EVs (sEVs), are lipid bilayer vesicles secreted by various cell types and play a key role in intercellular communication. These vesicles are promising tools for cancer immunotherapy owing to their biocompatibility, low immunogenicity, and capacity for targeted drug delivery. In this study, we aimed to assess the potential of engineered antigen-presenting EVs (AP-EVs) to selectively expand and differentiate antigen-specific CD4+ T cells. We engineered two types of AP-EVs: AP-EVs-Th1 expressing MHC class II, CD80, and interleukin (IL)-12 on their surface to promote Th1 differentiation, and AP-EVs-Th2 expressing MHC class II, CD80, and IL-4 to induce Th2 differentiation. In vitro experiments demonstrated that AP-EVs successfully induced the antigen-specific proliferation and differentiation of Th1 and Th2 cells, respectively. Notably, in vivo administration of AP-EVs-Th1 significantly enhanced the proliferation and differentiation of tumor antigen-specific Th1 cells, leading to robust anti-tumor effects in a murine melanoma model. These findings highlight the potential of AP-EVs-Th1 for cancer immunotherapy, particularly in augmenting CD4+ T cell responses. Furthermore, the versatility and adaptability of EV-based therapies make them beneficial for the development of personalized immunotherapeutic strategies for various cancer types, offering the advantages of targeted immune modulation, ease of use, and reduced risk compared to cell-based therapies.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2509969"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PEGylation technology: addressing concerns, moving forward. 聚乙二醇化技术：解决问题，向前发展。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-04-23 DOI: 10.1080/10717544.2025.2494775

Dmitri Simberg, Yechezkel Barenholz, Steve R Roffler, Katharina Landfester, Alexander V Kabanov, Seyed M Moghimi

{"title":"PEGylation technology: addressing concerns, moving forward.","authors":"Dmitri Simberg, Yechezkel Barenholz, Steve R Roffler, Katharina Landfester, Alexander V Kabanov, Seyed M Moghimi","doi":"10.1080/10717544.2025.2494775","DOIUrl":"https://doi.org/10.1080/10717544.2025.2494775","url":null,"abstract":"PEGylation technology, that is grafting of poly(ethylene glycol)(PEG) to biologics, vaccines and nanopharmaceuticals, has become a cornerstone of modern medicines with over thirty products used in the clinic. PEGylation of therapeutic proteins, nucleic acids and nanopharmaceuticals improves their stability, pharmacokinetic and biodistribution. While PEGylated medicines are safe in the majority of patients, there are growing concerns about the emergence of anti-PEG antibodies and their impact on the therapeutic efficacy of PEGylated medicines as well as broader immune responses, particularly in complement activation and hypersensitivity reactions. These concerns are beginning to scrutinize the future viability of PEGylation technology in medicine design. Here, we outline these concerns, encourage more efforts into looking for comprehensive scientific evidence on the role of anti-PEG antibodies in hypersensitivity reactions, discuss alternatives to PEG and propose strategies for moving PEGylation technology forward.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2494775"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983775","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}

引用次数: 0

Ophthalmic formulation of methotrexate: a strategy of using the self-assembled LacAC4A nanoparticles for non-invasive drug delivery to the ocular posterior segment. 甲氨蝶呤眼科配方：一种利用自组装LacAC4A纳米颗粒进行眼后段非侵入性给药的策略。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-05-29 DOI: 10.1080/10717544.2025.2509962

Xiao-Yun Hou, Xiao-Ling Zhang, An-Kang Ying, Yu-Xin Yue, Tao Yang, Dong-Sheng Guo, Zhi-Qing Li

{"title":"Ophthalmic formulation of methotrexate: a strategy of using the self-assembled LacAC4A nanoparticles for non-invasive drug delivery to the ocular posterior segment.","authors":"Xiao-Yun Hou, Xiao-Ling Zhang, An-Kang Ying, Yu-Xin Yue, Tao Yang, Dong-Sheng Guo, Zhi-Qing Li","doi":"10.1080/10717544.2025.2509962","DOIUrl":"10.1080/10717544.2025.2509962","url":null,"abstract":"Drug delivery to ocular posterior segment remains difficult due to the challenges imposed by dynamic and static ocular barriers, lesion point targeting, and off-target effect. In this study, a novel approach is demonstrated for non-invasive drug delivery to the ocular posterior segments using lactose-modified azocalix[4] arene (LacAC4A) as a supramolecular ocular drug delivery platform. LacAC4A contains azo groups and is covalently modified by lactose groups, which confers active targeting to the retina, and induces a hypoxic response. The immunomodulator methotrexate (MTX), which is commonly used in ophthalmology to treat immune system diseases such as uveitis, was also selected as a guest to prepare MTX@LacAC4A. The prepared LacAC4A and MTX@LacAC4A systems were characterized, then the internalization mechanisms and hypoxia response abilities were determined through flow cytometry and fluorescence imaging, respectively. Besides, the delivery route and efficiency were verified, and the safety profile of MTX@LacAC4A was evaluated in multiple dimensions. Importantly, it was found that the prepared MTX@LacAC4A exhibits good biocompatibility, can effectively reach the posterior segment, and demonstrates potential ophthalmic applications. These findings lay the grounds for the future development of non-invasive ocular posterior segment disease treatments based on the advanced use of LacAC4A as a drug delivery platform.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2509962"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173020","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}

引用次数: 0

Emerging liposomal therapies for diabetic retinopathy: a review of novel targeting approaches and advances in retinal health outcomes. 新出现的脂质体治疗糖尿病视网膜病变：新的靶向方法和视网膜健康结果的进展综述。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-05-29 DOI: 10.1080/10717544.2025.2509973

Ravi Parashar, Preeti K Suresh

引用次数: 0

Constructed transferrin receptor-targeted liposome for the delivery of fluvoxamine to improve prognosis in a traumatic brain injury mouse model. 构建转铁蛋白受体靶向脂质体用于输送氟伏沙明以改善创伤性脑损伤小鼠模型的预后。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-04-15 DOI: 10.1080/10717544.2025.2486840

Liang Mi, Jiangyuan Yuan, Yuxing Jiang, Yuqian Hu, Chuanxiang Lv, Yongqiang Xu, Mingqi Liu, Tao Liu, Xuanhui Liu, Jinhao Huang, Rongcai Jiang, Wei Quan

{"title":"Constructed transferrin receptor-targeted liposome for the delivery of fluvoxamine to improve prognosis in a traumatic brain injury mouse model.","authors":"Liang Mi, Jiangyuan Yuan, Yuxing Jiang, Yuqian Hu, Chuanxiang Lv, Yongqiang Xu, Mingqi Liu, Tao Liu, Xuanhui Liu, Jinhao Huang, Rongcai Jiang, Wei Quan","doi":"10.1080/10717544.2025.2486840","DOIUrl":"https://doi.org/10.1080/10717544.2025.2486840","url":null,"abstract":"The dysregulation of blood-brain barrier (BBB) activates pathological mechanisms such as neuroinflammation after traumatic brain injury (TBI), and glymphatic system dysfunction accelerates toxic waste accumulation after TBI. It is essential to find an effective way to inhibit inflammation and repair BBB and glymphatic system after TBI; however, effective and lasting drug therapy remains challenging because BBB severely prevents drugs from being delivered to central nervous system. Transferrin receptors (TfRs) are mainly expressed on brain capillary endothelial cells. Here, we report a TfR-targeted nanomedicine for TBI treatment by penetrating BBB and delivering fluvoxamine (Flv). The TfR-targeted polypeptide liposome loaded with Flv (TPL-Flv) implements cell targeting ability on human umbilical vein endothelial cells (HUVECs) in vitro detected by flow cytometry, and drug safety was proved through cell viability analysis and blood routine and biochemistry analysis. Afterwards, we established a controlled cortical impact model to explore TPL-Flv administration effects on TBI mice. We confirmed that TPL-Flv could stimulate CXCR4/SDF-1 signaling pathway, activate Treg cells, and inhibit inflammation after TBI. TPL-Flv treatment also alleviated BBB disruption and restored aquaporin-4 (AQP4) polarization, as well as reversed glymphatic dysfunction. Furthermore, TPL-Flv accomplished remarkable improvement of motor and cognitive functions. These findings demonstrate that TPL-Flv can effectively cross BBB and achieve drug delivery to cerebral tissue, validating its potential to improve therapeutic outcomes for TBI.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2486840"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977814","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}

引用次数: 0

Antigenic peptide delivery to antigen-presenting cells using a CD40-coiled coil affinity-based platform. 抗原肽递送到抗原呈递细胞使用cd40线圈亲和为基础的平台。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-05-26 DOI: 10.1080/10717544.2025.2486340

Barnabas Nyesiga, Karin Hägerbrand, Laura Varas, Anette Gjörloff Wingren, Mats Ohlin, Peter Ellmark, Laura von Schantz

{"title":"Antigenic peptide delivery to antigen-presenting cells using a CD40-coiled coil affinity-based platform.","authors":"Barnabas Nyesiga, Karin Hägerbrand, Laura Varas, Anette Gjörloff Wingren, Mats Ohlin, Peter Ellmark, Laura von Schantz","doi":"10.1080/10717544.2025.2486340","DOIUrl":"10.1080/10717544.2025.2486340","url":null,"abstract":"Delivery of antigenic peptides to antigen presenting cells (APCs) such as dendritic cells (DCs) using monoclonal antibodies (mAbs) is an attractive approach to evoke antigen-specific T cell activation and improve drug efficacy. Peptide linkage to mAbs has previously been achieved through genetic fusion, chemical conjugation, nano-engineered platforms and high affinity peptides. In this study, we have developed a flexible antibody-peptide linking technology using oppositely charged coiled coil domains to non-covalently link peptides to mAbs. The technology comprises (1) an anti-CD40 mAb connected with negatively charged E domains and (2) an immunogenic OVA peptide (SIINFEKL) from ovalbumin used as a model antigenic peptide fused with positively charged K domains. Combining these constructs leads to the formation of complexes that can be targeted to CD40 expressed on cells. Proof of concept antibody constructs connected with E domains generated from transient expressions exhibited good manufacturability, binding, and stability attributes comparable to a control mAb. Also, optimal repeat lengths for coiled-coil oligomerization domains were identified in these studies. Binding kinetics studies showed that connecting E domains to mAbs do not impede Fc gamma and neonatal receptor interactions. Additionally, formation of stable complexes capable of binding CD40 expressing cells was demonstrated in vitro. In vivo functionality evaluations showed that treatment of human CD40 transgenic mice with complexes elicited expansion of OVA peptide-specific CD8+ T cells and potent antitumor effects superior to peptide monotherapies. Overall, these findings demonstrate that the technology has great potential for application as an in vivo tool for antigenic peptide delivery.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2486340"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141815","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}

引用次数: 0

Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia. 机器学习辅助设计免疫调节脂质纳米颗粒，用于递送mRNA以使过度激活的小胶质细胞再极化。

IF 6.5 2区医学

Drug Delivery Pub Date : 2025-12-01 Epub Date: 2025-03-03 DOI: 10.1080/10717544.2025.2465909

Mehrnoosh Rafiei, Akbar Shojaei, Ying Chau

{"title":"Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia.","authors":"Mehrnoosh Rafiei, Akbar Shojaei, Ying Chau","doi":"10.1080/10717544.2025.2465909","DOIUrl":"10.1080/10717544.2025.2465909","url":null,"abstract":"Regulating inflammatory microglia presents a promising strategy for treating neurodegenerative and autoimmune disorders, yet effective therapeutic agents delivery to these cells remains a challenge. This study investigates modified lipid nanoparticles (LNP) for mRNA delivery to hyperactivated microglia, particularly those with pro-inflammatory characteristics, utilizing supervised machine learning (ML) classifiers. We developed and screened a library of 216 LNP formulations with varying lipid compositions, N/P ratios, and hyaluronic acid (HA) modifications. The transfection efficiency of eGFP mRNA was assessed in the BV-2 murine microglia cell line under different immunological states, including resting and activated conditions (LPS-activated and IL4/IL13-activated). ML-guided morphometric analysis tracked the phenotypes of various microglia subtypes before and after transfection. Four supervised ML classifiers were investigated to predict transfection efficiency and phenotypic changes based on LNP design parameters. The Multi-Layer Perceptron (MLP) neural network emerged as the best-performing model, achieving weighted F1-scores ≥0.8. While it accurately predicted responses from LPS-activated and resting cells, it struggled with IL4/IL13-activated cells. The MLP model was validated by predicting the performance of four unseen LNP formulations delivering eGFP mRNA to LPS-activated BV2 cells. HA-LNP2 emerged as optimal formulation for delivering target IL10 mRNA, effectively suppressing inflammatory phenotypes, evidenced by shifts in cell morphology, increased IL10 expression, and reduced TNF-α levels. We also evaluated HA-LNP2 on LPS-activated human iPSC-derived microglia, confirming its efficacy in modulating inflammatory responses. This study highlights the potential of tailored LNP design and ML techniques to enhance mRNA therapy for neuroinflammatory disorders by leveraging carrier's immunogenic properties to modulate microglial responses.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"32 1","pages":"2465909"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540603","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}

引用次数: 0