The effect of nanoparticle size, shape, and surface properties on cellular uptake has been extensively investigated for its basic science and translational implications. Recently, softness is emerging as a design parameter for modulating the interaction of nanoparticles with cells and the biological microenvironment. Here, circular, quadrangular, and elliptical polymeric nanoconstructs of different sizes are realized with a Young’s modulus ranging from ∼100 kPa (soft) to 10 MPa (rigid). The interaction of these nanoconstructs with professional phagocytic cells is assessed via confocal microscopy and flow cytometry analyses. Regardless of the size and shape, softer nanoconstructs evade cellular uptake up to 5 times more efficiently, by bone-marrow-derived monocytes, as compared to rigid nanoconstructs. Soft circular and quadrangular nanoconstructs are equally uptaken by professional phagocytic cells (<15%); soft elliptical particles are more avidly internalized (<60%) possibly because of the larger size and elongated shape, whereas over 70% of rigid nanoconstructs of any shape and size are uptaken. Inhibition of actin polymerization via cytochalasin D reduces the internalization propensity for all nanoconstruct types. High-resolution live cell microscopy documents that soft nanoconstructs mostly establish short-lived (<30 s) interactions with macrophages, thus diminishing the likelihood of recognition and internalization. The bending stiffness is identified as a discriminating factor for internalization, whereby particles with a bending stiffness slightly higher than cells would more efficiently oppose internalization as compared to stiffer or softer particles. These results confirm that softness is a key parameter in modulating the behavior of nanoparticles and are expected to inspire the design of more efficient nanoconstructs for drug delivery, biomedical imaging, and immunomodulatory therapies.

中文翻译：

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通过调整纳米结构的柔软度来调节吞噬细胞的隔离

纳米颗粒的大小，形状和表面性质对细胞摄取的影响已被广泛研究，因为它具有基础科学和转化意义。近年来，柔软性正逐渐成为一种设计参数，用于调节纳米颗粒与细胞和生物微环境之间的相互作用。在这里，实现了具有不同尺寸的圆形，四边形和椭圆形的聚合物纳米结构，其杨氏模量范围从约100 kPa（软）到10 MPa（刚性）。这些纳米结构与专业吞噬细胞的相互作用通过共聚焦显微镜和流式细胞仪分析。无论大小和形状如何，与刚性纳米结构相比，较软的纳米结构通过骨髓衍生的单核细胞逃避细胞吸收的效率最高可提高5倍。专业的吞噬细胞（<15％）同样摄取柔软的圆形和四边形纳米结构。柔软的椭圆形颗粒更容易被内在化（<60％），这可能是由于其较大的尺寸和细长的形状，而超过70％的任何形状和尺寸的刚性纳米结构均被吸收。通过抑制肌动蛋白聚合细胞松弛素D降低了所有纳米结构类型的内在化倾向。高分辨率的活细胞显微镜检查文件显示，软纳米结构主要与巨噬细胞建立了短暂的（<30 s）相互作用，从而降低了识别和内化的可能性。弯曲刚度被认为是内在化的判别因素，因此，与刚度或更软的粒子相比，弯曲刚度略高于泡孔的颗粒将更有效地反对内在化。这些结果证实，柔软度是调节纳米颗粒行为的关键参数，并有望激发设计更有效的纳米结构用于药物输送，生物医学成像和免疫调节疗法。