Nanoparticle elasticity directs tumor uptake.
Nanoparticle elasticity directs tumor uptake.
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DOI：
10.1038/s41467-017-02588-9
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发表时间：
2018-01-09
影响因子：
16.6
通讯作者：
Moses MA
中科院分区：
文献类型：
--
作者：
Guo P;Liu D;Subramanyam K;Wang B;Yang J;Huang J;Auguste DT;Moses MA
到目前为止，弹性在药物输送中的作用仍然难以捉摸，因为无法在不影响化学的情况下测量微观力学和改变流变学。在此，我们描述了纳米磷脂凝胶(NLGS)的体外细胞摄取和体内肿瘤摄取。NLGS由包裹着藻酸盐核心的相同的脂双层组成，具有可调节的弹性。用原子力显微镜评价了NLGS的弹性，发现它们的杨氏模数在45 ± 9~19,000 ± 5 kpa之间。肿瘤和非肿瘤细胞对软性NLGS(杨氏模数1.6 Mpa)的摄取显著高于弹性细胞(杨氏模数13.8 Mpa)。在原位乳腺肿瘤模型中，软性NLGS在肿瘤中积聚明显更多，而弹性NLGS优先在肝脏积聚。我们的发现表明，颗粒弹性引导肿瘤的聚集，这表明它可能是一个设计参数，以提高肿瘤的输送效率。纳米颗粒弹性被认为在药物输送中起着重要作用，但研究很少。在这里，作者使用模数可调的纳米凝胶来研究颗粒弹性对体外细胞摄取和体内肿瘤摄取的影响，发现较硬的颗粒不容易内化。
To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Herein, we describe the in vitro cellular uptake and in vivo tumor uptake of nanolipogels (NLGs). NLGs are composed of identical lipid bilayers encapsulating an alginate core, with tunable elasticity. The elasticity of NLGs was evaluated by atomic force microscopy, which demonstrated that they exhibit Young’s moduli ranging from 45 ± 9 to 19,000 ± 5 kPa. Neoplastic and non-neoplastic cells exhibited significantly greater uptake of soft NLGs (Young’s modulus <1.6 MPa) relative to their elastic counterparts (Young’s modulus >13.8 MPa). In an orthotopic breast tumor model, soft NLGs accumulated significantly more in tumors, whereas elastic NLGs preferentially accumulated in the liver. Our findings demonstrate that particle elasticity directs tumor accumulation, suggesting that it may be a design parameter to enhance tumor delivery efficiency. Nanoparticle elasticity is thought to play an important role in drug delivery, but is little studied. Here, the authors use nanolipogels with tunable moduli to study the effect of particle elasticity on in vitro cellular uptake and in vivo tumor uptake, finding that stiffer particles are not as easily internalized.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
38.3
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Anselmo, Aaron C.;Zhang, Mengwen;Mitragotri, Samir
通讯作者：
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影响因子：
14
作者：
Guo P;You JO;Yang J;Moses MA;Auguste DT
通讯作者：
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