Injectable nanomaterials that interact with the host immune system without surgical intervention present spatially anchored complements to cell transplantation and could offer improved pharmacokinetics compared to systemic cytokine therapy. Here we demonstrate fabrication of high aspect ratio polycaprolactone nanowires coupled with cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. These structures are fabricated using a nanotemplating technique that allows for tunability of particle dimensions and utilize a straightforward maleimide conjugation chemistry to allow site-specific coupling to proteins. Nanowires are well tolerated in vivo and incite minimal inflammatory infiltrate. Nanowires conjugated with antibodies were designed to capture and potentiate endogenous interleukin-2 (IL-2), an important leukocyte activating cytokine. Together these nanowire-antibody matrices were capable of localizing endogenous IL-2 in the skin and activated targeted specific natural killer and T cell subsets, demonstrating both tissue- and cell-specific immune activation. These self-assembling nanowire matrices show promise as scaffolds to present engineered, local receptor–ligand interactions for cytokine-mediated disease.

中文翻译：

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可注射的聚合物细胞因子结合纳米线是有效的组织特异性免疫调节剂。

与宿主免疫系统相互作用而无需手术干预的可注射纳米材料，在空间上锚定了细胞移植的补体，与全身性细胞因子疗法相比，可提供更高的药代动力学。在这里，我们展示了高纵横比的聚己内酯纳米线与细胞因子结合抗体的结合，当注入皮下空间时，细胞因子结合抗体可组装成多孔基质。这些结构是使用纳米模板技术制造的，该技术可实现颗粒尺寸的可调性，并利用直接的马来酰亚胺共轭化学技术实现与蛋白质的位点特异性偶联。纳米线在体内具有良好的耐受性并引起极少的炎性浸润。与抗体缀合的纳米线被设计为捕获并增强内源性白介素2（IL-2）（一种重要的白细胞激活细胞因子）。这些纳米线抗体基质一起能够定位皮肤中的内源性IL-2并激活靶向的特定自然杀手和T细胞亚群，从而证明了组织特异性和细胞特异性免疫激活。这些自组装的纳米线基质有望作为支架展示细胞因子介导的疾病的工程化，局部受体-配体相互作用。