Ameruoso Andrea, Palomba Roberto, Palange Anna Lisa, Cervadoro Antonio, Lee Aeju, Di Mascolo Daniele, Decuzzi Paolo
Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genoa, Italy.
International Research Organization for Advanced Science and Technology (IROAST), Kumamoto University, Kumamoto, Kumamoto Prefecture, Japan.
Front Immunol. 2017 Oct 31;8:1411. doi: 10.3389/fimmu.2017.01411. eCollection 2017.
Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer's disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic--glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks. First, the internalization propensity in macrophages of both nanoparticles was assessed cytofluorimetric and confocal microscopy analyses, demonstrating that SPNs are by far more rapidly taken up as compared to DPNs (99.6 ± 0.11 vs 14.4 ± 0.06%, within 24 h). Then, Curcumin-loaded SPNs (Curc-SPNs) were realized by encapsulating Curcumin, a natural anti-inflammatory molecule, within the PLGA core of SPNs. Finally, Curc-SPNs were shown to diminish up to 6.5-fold the production of pro-inflammatory cytokines-IL-1β; IL-6, and TNF-α-in macrophages stimulated amyloid-β fibers. Although more sophisticated models and systematic analyses on the blood-brain barrier permeability are critically needed, these findings hold potential in the development of nanoparticles for modulating inflammation in AD.
炎症是包括动脉粥样硬化、癌症、肥胖症和神经退行性疾病在内的多种疾病的常见特征。在阿尔茨海默病（AD）中，越来越多的证据直接将神经元损伤与髓样脑细胞（如小胶质细胞）的炎症联系起来。在此，设计并表征了聚合物纳米颗粒，用于将抗炎分子递送至通过与淀粉样β纤维直接孵育而被刺激的巨噬细胞。使用聚乳酸-乙醇酸共聚物（PLGA）、聚乙二醇（PEG）和脂质链作为构建模块，合成了200纳米的球形聚合物纳米结构（SPN）和1000纳米的盘状聚合物纳米结构（DPN）。首先，通过细胞荧光分析和共聚焦显微镜分析评估了两种纳米颗粒在巨噬细胞中的内化倾向，结果表明，与DPN相比，SPN的摄取速度要快得多（24小时内分别为99.6±0.11%和14.4±0.06%）。然后，通过将天然抗炎分子姜黄素封装在SPN的PLGA核心内，制备了负载姜黄素的SPN（Curc-SPN）。最后，结果显示Curc-SPN可将经淀粉样β纤维刺激的巨噬细胞中促炎细胞因子IL-1β、IL-6和TNF-α的产生减少多达6.5倍。尽管迫切需要更复杂的血脑屏障通透性模型和系统分析，但这些发现为开发用于调节AD炎症的纳米颗粒具有潜在意义。
