{"title":"PLGA纳米颗粒介导的抗炎基因传递治疗神经性疼痛。","authors":"Boomin Choi, Subeen Lee, Seohyun Chung, Ellane Eda Barcelona, Jinpyo Hong, Sung Joong Lee","doi":"10.1080/17435889.2025.2487410","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to mitigate neuropathic pain behavior in a sciatic nerve transection (SNT)-induced mouse model by delivering anti-inflammatory cytokines - interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta 1 (TGF-β1) - via poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).</p><p><strong>Materials & methods: </strong>Upon gene delivery of IL-4, IL-10, and TGF- β1, the anti-inflammatory effects and induction of microglia M2 polarization were evaluated. Plasmid (IL-4, IL-10, and TGF-β1)-encapsulated PLGA NPs (PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1) were synthesized and characterized for size, zeta potential, cellular toxicity, and cellular uptake. The analgesic effect of anti-inflammatory gene delivery using PLGA NPs was then assessed in a mouse model of neuropathic pain.</p><p><strong>Results: </strong>Gene delivery of IL-4, IL-10, and TGF-β1 showed a significant anti-inflammatory effect in LPS-treated cells and IL-4 strongly promoted microglia M2 polarization in vitro. PLGA NPs successfully delivered the anti-inflammatory cytokine-coding genes into mouse spinal cord cells, specifically targeting microglia. PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1 NPs produced analgesic effects in a SNT-induced mouse neuropathic pain model. Notably, PLGA@IL-4 demonstrated the most effective and remarkably long-lasting analgesic effect, strongly enhancing microglia M2 polarization in spinal cord microglia.</p><p><strong>Conclusion: </strong>Gene therapy using PLGA NPs for overexpression of anti-inflammatory cytokines could be a promising strategy for the treatment of neuropathic pain.</p>","PeriodicalId":74240,"journal":{"name":"Nanomedicine (London, England)","volume":" ","pages":"1-12"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PLGA nanoparticle-mediated anti-inflammatory gene delivery for the treatment of neuropathic pain.\",\"authors\":\"Boomin Choi, Subeen Lee, Seohyun Chung, Ellane Eda Barcelona, Jinpyo Hong, Sung Joong Lee\",\"doi\":\"10.1080/17435889.2025.2487410\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>This study aimed to mitigate neuropathic pain behavior in a sciatic nerve transection (SNT)-induced mouse model by delivering anti-inflammatory cytokines - interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta 1 (TGF-β1) - via poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).</p><p><strong>Materials & methods: </strong>Upon gene delivery of IL-4, IL-10, and TGF- β1, the anti-inflammatory effects and induction of microglia M2 polarization were evaluated. Plasmid (IL-4, IL-10, and TGF-β1)-encapsulated PLGA NPs (PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1) were synthesized and characterized for size, zeta potential, cellular toxicity, and cellular uptake. The analgesic effect of anti-inflammatory gene delivery using PLGA NPs was then assessed in a mouse model of neuropathic pain.</p><p><strong>Results: </strong>Gene delivery of IL-4, IL-10, and TGF-β1 showed a significant anti-inflammatory effect in LPS-treated cells and IL-4 strongly promoted microglia M2 polarization in vitro. PLGA NPs successfully delivered the anti-inflammatory cytokine-coding genes into mouse spinal cord cells, specifically targeting microglia. PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1 NPs produced analgesic effects in a SNT-induced mouse neuropathic pain model. Notably, PLGA@IL-4 demonstrated the most effective and remarkably long-lasting analgesic effect, strongly enhancing microglia M2 polarization in spinal cord microglia.</p><p><strong>Conclusion: </strong>Gene therapy using PLGA NPs for overexpression of anti-inflammatory cytokines could be a promising strategy for the treatment of neuropathic pain.</p>\",\"PeriodicalId\":74240,\"journal\":{\"name\":\"Nanomedicine (London, England)\",\"volume\":\" \",\"pages\":\"1-12\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine (London, England)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17435889.2025.2487410\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine (London, England)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17435889.2025.2487410","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
PLGA nanoparticle-mediated anti-inflammatory gene delivery for the treatment of neuropathic pain.
Aim: This study aimed to mitigate neuropathic pain behavior in a sciatic nerve transection (SNT)-induced mouse model by delivering anti-inflammatory cytokines - interleukin-4 (IL-4), interleukin-10 (IL-10), and transforming growth factor-beta 1 (TGF-β1) - via poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).
Materials & methods: Upon gene delivery of IL-4, IL-10, and TGF- β1, the anti-inflammatory effects and induction of microglia M2 polarization were evaluated. Plasmid (IL-4, IL-10, and TGF-β1)-encapsulated PLGA NPs (PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1) were synthesized and characterized for size, zeta potential, cellular toxicity, and cellular uptake. The analgesic effect of anti-inflammatory gene delivery using PLGA NPs was then assessed in a mouse model of neuropathic pain.
Results: Gene delivery of IL-4, IL-10, and TGF-β1 showed a significant anti-inflammatory effect in LPS-treated cells and IL-4 strongly promoted microglia M2 polarization in vitro. PLGA NPs successfully delivered the anti-inflammatory cytokine-coding genes into mouse spinal cord cells, specifically targeting microglia. PLGA@IL-4, PLGA@IL-10, and PLGA@TGF-β1 NPs produced analgesic effects in a SNT-induced mouse neuropathic pain model. Notably, PLGA@IL-4 demonstrated the most effective and remarkably long-lasting analgesic effect, strongly enhancing microglia M2 polarization in spinal cord microglia.
Conclusion: Gene therapy using PLGA NPs for overexpression of anti-inflammatory cytokines could be a promising strategy for the treatment of neuropathic pain.
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