S A Lim, S Chen, I Suzuki, K Lambaren, A Soleimani, N Ho, M Mousavi, E J Chung
{"title":"利用微针递送和保存自然杀伤细胞衍生的细胞外囊泡。","authors":"S A Lim, S Chen, I Suzuki, K Lambaren, A Soleimani, N Ho, M Mousavi, E J Chung","doi":"10.1021/acsbiomaterials.5c00760","DOIUrl":null,"url":null,"abstract":"<p><p>Natural killer cell-derived extracellular vesicles (NK-EVs) have demonstrated anti-inflammatory properties similar to those of their parent cells. EVs have been commonly delivered via intravenous (IV) administration, which can be invasive and is not ideal for chronic treatment. Another limitation of nanotherapy is its storage requirements, as EVs are commonly stored at -80 °C to preserve EV cargo and stability. In order to address these limitations, we explored dissolvable microneedles (MNs) as a promising alternative method for the administration of EVs. MNs have been used to deliver drugs, vaccines, and biomolecules, offering a convenient, noninvasive route of administration while preserving the therapeutic efficacy of EVs for extended periods, even at room temperature. Thus, we hypothesize that MN has the potential to sustain NK-EV stability and successfully deliver NK-EVs with minimal invasion. To test our hypothesis, we first developed an optimal MN formulation composed of hyaluronic acid and trehalose, both protein-protective materials that are biocompatible and biodegradable. After preparing MNs, we evaluated their stiffness, EV release profile, and ability to puncture pig skin. Additionally, the long-term storage stability of the EVs in MNs in inflammatory models in vitro and in vivo was evaluated. The MN successfully maintained EV efficacy even after storage after six months at room temperature, reducing the pro-inflammatory cytokine IL-6 by about 70% in inflamed human fibroblast cells relative to nontreated groups. Furthermore, EV-loaded MN treatment reduced both pro-inflammatory cytokines (IL-6 and TNFα) and psoriasis markers (Ki67 and IL-17) expression in a psoriasis model of chronic inflammation by about 40% compared to nontreated groups. Herein, our MN demonstrates the potential for easy-to-administer NK-EV therapies with long-term storage capabilities that preserve the NK-EV's anti-inflammatory properties.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Harnessing Microneedles for Delivery and Preservation of Natural Killer Cell-Derived Extracellular Vesicles.\",\"authors\":\"S A Lim, S Chen, I Suzuki, K Lambaren, A Soleimani, N Ho, M Mousavi, E J Chung\",\"doi\":\"10.1021/acsbiomaterials.5c00760\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Natural killer cell-derived extracellular vesicles (NK-EVs) have demonstrated anti-inflammatory properties similar to those of their parent cells. EVs have been commonly delivered via intravenous (IV) administration, which can be invasive and is not ideal for chronic treatment. Another limitation of nanotherapy is its storage requirements, as EVs are commonly stored at -80 °C to preserve EV cargo and stability. In order to address these limitations, we explored dissolvable microneedles (MNs) as a promising alternative method for the administration of EVs. MNs have been used to deliver drugs, vaccines, and biomolecules, offering a convenient, noninvasive route of administration while preserving the therapeutic efficacy of EVs for extended periods, even at room temperature. Thus, we hypothesize that MN has the potential to sustain NK-EV stability and successfully deliver NK-EVs with minimal invasion. To test our hypothesis, we first developed an optimal MN formulation composed of hyaluronic acid and trehalose, both protein-protective materials that are biocompatible and biodegradable. After preparing MNs, we evaluated their stiffness, EV release profile, and ability to puncture pig skin. Additionally, the long-term storage stability of the EVs in MNs in inflammatory models in vitro and in vivo was evaluated. The MN successfully maintained EV efficacy even after storage after six months at room temperature, reducing the pro-inflammatory cytokine IL-6 by about 70% in inflamed human fibroblast cells relative to nontreated groups. Furthermore, EV-loaded MN treatment reduced both pro-inflammatory cytokines (IL-6 and TNFα) and psoriasis markers (Ki67 and IL-17) expression in a psoriasis model of chronic inflammation by about 40% compared to nontreated groups. Herein, our MN demonstrates the potential for easy-to-administer NK-EV therapies with long-term storage capabilities that preserve the NK-EV's anti-inflammatory properties.</p>\",\"PeriodicalId\":8,\"journal\":{\"name\":\"ACS Biomaterials Science & Engineering\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Biomaterials Science & Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1021/acsbiomaterials.5c00760\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.5c00760","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Harnessing Microneedles for Delivery and Preservation of Natural Killer Cell-Derived Extracellular Vesicles.
Natural killer cell-derived extracellular vesicles (NK-EVs) have demonstrated anti-inflammatory properties similar to those of their parent cells. EVs have been commonly delivered via intravenous (IV) administration, which can be invasive and is not ideal for chronic treatment. Another limitation of nanotherapy is its storage requirements, as EVs are commonly stored at -80 °C to preserve EV cargo and stability. In order to address these limitations, we explored dissolvable microneedles (MNs) as a promising alternative method for the administration of EVs. MNs have been used to deliver drugs, vaccines, and biomolecules, offering a convenient, noninvasive route of administration while preserving the therapeutic efficacy of EVs for extended periods, even at room temperature. Thus, we hypothesize that MN has the potential to sustain NK-EV stability and successfully deliver NK-EVs with minimal invasion. To test our hypothesis, we first developed an optimal MN formulation composed of hyaluronic acid and trehalose, both protein-protective materials that are biocompatible and biodegradable. After preparing MNs, we evaluated their stiffness, EV release profile, and ability to puncture pig skin. Additionally, the long-term storage stability of the EVs in MNs in inflammatory models in vitro and in vivo was evaluated. The MN successfully maintained EV efficacy even after storage after six months at room temperature, reducing the pro-inflammatory cytokine IL-6 by about 70% in inflamed human fibroblast cells relative to nontreated groups. Furthermore, EV-loaded MN treatment reduced both pro-inflammatory cytokines (IL-6 and TNFα) and psoriasis markers (Ki67 and IL-17) expression in a psoriasis model of chronic inflammation by about 40% compared to nontreated groups. Herein, our MN demonstrates the potential for easy-to-administer NK-EV therapies with long-term storage capabilities that preserve the NK-EV's anti-inflammatory properties.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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