Near-infrared light-controlled regulation of intracellular calcium to modulate macrophage polarization
Near-infrared light-controlled regulation of intracellular calcium to modulate macrophage polarization
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近红外光控制细胞内钙调节巨噬细胞极化
DOI：
10.1016/j.biomaterials.2018.03.007
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发表时间：
2018-09-01
期刊：
影响因子：
14
通讯作者：
Bian, Liming
中科院分区：
文献类型：
--
作者：
Kang, Heemin;Zhang, Kunyu;Bian, Liming
巨噬细胞是一种多功能免疫细胞，具有多种生理功能，如对抗感染、影响疾病进展、维持体内平衡和组织再生等。巨噬细胞可以被诱导采用不同的极化表型，如经典激活的促炎(M1)表型或交替激活的抗炎和促进愈合(M2)表型，以执行多样化和动态的免疫功能。然而，巨噬细胞极化不平衡可导致多种病理改变，如动脉粥样硬化、肥胖、肿瘤和哮喘。因此，远程控制巨噬细胞表型的能力对于成功治疗许多涉及巨噬细胞的病理疾病非常重要。在这项研究中，我们开发了一种基于上转换纳米颗粒(UCNP)的光响应纳米载体，用于近红外(NIR)光介导的细胞内钙水平控制，以调节巨噬细胞的极化。用介孔二氧化硅(UCNP@mSiO(2))包覆了UCNP，在介孔二氧化硅中负载了钙离子调节剂，既可以供应钙离子，也可以消耗钙离子。UCNP@mSiO(2)通过环糊精-金刚烷主-客体络合，通过光解连接物与Arg-Gly-Asp(RGD)多肽分子帽的串联偶联进行化学修饰。RGD帽起到耐光门结构的作用，控制钙调节剂的释放，促进细胞摄取UCNP@mSiO(2)纳米载体。UCNP@mSiO(2)在近红外光激发下的上转换紫外光发射触发了CaP的裂解和细胞内钙调节剂的释放，从而允许对细胞内钙水平的时间调节。近红外光透过皮肤组织，分别通过提高或耗尽细胞内钙水平，促进巨噬细胞M1或M2极化。据我们所知，这是近红外光介导的远程控制巨噬细胞极化的第一次演示。这种光响应型纳米载体通过近红外光控制的巨噬细胞极化，提供了远程操纵体内免疫功能的可能性，例如炎症或组织再生。(C)2018爱思唯尔有限公司。保留所有权利。
Macrophages are multifunctional immune cells with diverse physiological functions such as fighting against infection, influencing progression of pathologies, maintaining homeostasis, and regenerating tissues. Macrophages can be induced to adopt distinct polarized phenotypes, such as classically activated pro-inflammatory (M1) phenotypes or alternatively activated anti-inflammatory and pro-healing (M2), to execute diverse and dynamic immune functions. However, unbalanced polarizations of macrophage can lead to various pathologies, such as atherosclerosis, obesity, tumor, and asthma. Thus, the capability to remotely control macrophage phenotypes is important to the success of treating many pathological conditions involving macrophages. In this study, we developed an upconversion nanoparticle (UCNP)-based photoresponsive nanocarrier for near-infrared (NIR) light-mediated control of intracellular calcium levels to regulate macrophage polarization. UCNP was coated with mesoporous silica (UCNP@mSiO(2)), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO(2) was chemically modified through serial coupling of photocleavable linker and Arg-Gly-Asp (RGD) peptide bearing molecular cap via cyclodextrin-adamantine host-guest complexation. The RGD-bearing cap functioned as the photolabile gating structure to control the release of calcium regulators and facilitated the cellular uptake of UCNP@mSiO(2) nanocarrier. The upconverted UV light emission from the UCNP@mSiO(2) under NIR light excitation triggered the cleavage of cap and intracellular release of calcium regulators, thereby allowing temporal regulation on the intracellular calcium levels. Application of NIR light through skin tissue promoted M1 or M2 polarization of macrophages, by elevating or depleting intracellular calcium levels, respectively. To the best of our knowledge, this is the first demonstration of NIR light-mediated remote control on macrophage polarization. This photoresponsive nanocarrier offers the potential to remotely manipulate in vivo immune functions, such as inflammation or tissue regeneration, via NIR light-controlled macrophage polarization. (C) 2018 Elsevier Ltd. All rights reserved.