The physicochemical properties of nanoparticles (size, charge, and surface chemistry, etc.) influence their biological functions often in complex and poorly understood ways. This complexity is compounded when the nanostructures involved have variable mechanical properties. Here, we report the synthesis of liquid-filled silica nanocapsules (SNCs, ∼ 150 nm) having a wide range of stiffness (with Young’s moduli ranging from 704 kPa to 9.7 GPa). We demonstrate a complex trade-off between nanoparticle stiffness and the efficiencies of both immune evasion and passive/active tumor targeting. Soft SNCs showed 3 times less uptake by macrophages than stiff SNCs, while the uptake of PEGylated SNCs by cancer cells was independent of stiffness. In addition, the functionalization of stiff SNCs with folic acid significantly enhanced their receptor-mediated cellular uptake, whereas little improvement for the soft SNCs was conferred. Further in vivo experiments confirmed these findings and demonstrated the critical role of nanoparticle mechanical properties in regulating their interactions with biological systems.

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了解纳米囊的机械性能对被动和主动肿瘤靶向的影响

纳米粒子的物理化学性质（大小，电荷和表面化学等））通常以复杂且鲜为人知的方式影响其生物学功能。当涉及的纳米结构具有可变的机械性能时，这种复杂性变得更加复杂。在这里，我们报道了具有宽范围的刚度（杨氏模量从704 kPa到9.7 GPa）的液体填充的二氧化硅纳米胶囊（〜150 nm）的合成。我们证明了纳米粒子的刚度和免疫逃避和被动/主动肿瘤靶向效率之间的复杂权衡。软SNC显示出的巨噬细胞摄取量比刚性SNC少3倍，而癌细胞对PEG化SNC的摄取与刚性无关。此外，用叶酸将刚性SNCs功能化可显着增强其受体介导的细胞摄取，而对软SNCs几乎没有改善。进一步体内实验证实了这些发现，并证明了纳米粒子机械性能在调节其与生物系统的相互作用中的关键作用。