Choi Boomin, Lee Subeen, Chung Seohyun, Barcelona Ellane Eda, Hong Jinpyo, Lee Sung Joong
Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Interdisciplinary Program in Neuroscience, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
Nanomedicine (Lond). 2025 May;20(9):943-954. doi: 10.1080/17435889.2025.2487410. Epub 2025 Apr 5.
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.
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.
Gene therapy using PLGA NPs for overexpression of anti-inflammatory cytokines could be a promising strategy for the treatment of neuropathic pain.
本研究旨在通过聚（d，l-乳酸-乙醇酸）（PLGA）纳米颗粒（NPs）递送抗炎细胞因子——白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1），减轻坐骨神经横断（SNT）诱导的小鼠模型中的神经性疼痛行为。
在递送IL-4、IL-10和TGF-β1基因后，评估其抗炎作用和对小胶质细胞M2极化的诱导作用。合成了包裹质粒（IL-4、IL-10和TGF-β1）的PLGA NPs（PLGA@IL-4、PLGA@IL-10和PLGA@TGF-β1），并对其大小、zeta电位、细胞毒性和细胞摄取进行了表征。然后在神经性疼痛小鼠模型中评估使用PLGA NPs进行抗炎基因递送的镇痛效果。
IL-4、IL-10和TGF-β1基因递送在脂多糖处理的细胞中显示出显著的抗炎作用，并且IL-4在体外强烈促进小胶质细胞M2极化。PLGA NPs成功地将抗炎细胞因子编码基因递送至小鼠脊髓细胞，特别是靶向小胶质细胞。PLGA@IL-4、PLGA@IL-10和PLGA@TGF-β1 NPs在SNT诱导的小鼠神经性疼痛模型中产生了镇痛作用。值得注意的是，PLGA@IL-4表现出最有效且持久的镇痛作用，强烈增强了脊髓小胶质细胞中的小胶质细胞M2极化。
使用PLGA NPs进行抗炎细胞因子过表达的基因治疗可能是治疗神经性疼痛的一种有前景的策略。
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