An in silicoanalysis of nanoparticle/cell diffusive transfer: Application to nano-artificial antigen-presenting cell:T-cell interaction

An in silicoanalysis of nanoparticle/cell diffusive transfer: Application to nano-artificial antigen-presenting cell:T-cell interaction
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DOI:
10.1016/j.nano.2014.12.019
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发表时间:
2015-05-01
影响因子:
5.4
通讯作者:
Fahmy, Tarek M.
Fahmy, Tarek M.
中科院分区:
医学2区
文献类型:
--
作者:
Labowsky, Michael;Lowenthal, Justin;Fahmy, Tarek M.

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经t细胞抗原修饰并包封免疫刺激或免疫抑制因子的聚合纳米颗粒(nano-paAPCs)可作为人工抗原提呈细胞,递送至循环免疫细胞,从而提高包封药物或细胞因子对抗原特异性t细胞的选择性递送。将这些纳米颗粒包裹的药物旁分泌递送至邻近细胞有助于持续递送,从而降低总体给药剂量,从而提高整体药物疗效,同时降低多效因子的毒性。在细胞附近或嵌入细胞的纳米颗粒周围积聚的释放剂的局部浓度在数学上知之甚少。计算这些浓度场是为了了解这些纳米paapc系统的旁分泌功效。如果颗粒嵌入细胞膜,可能会发生显著的因子积累,这可以解释观察到的实验数据,即增强t细胞活化和纳米颗粒介导的药物递送过程中对非内化细胞靶标的改善。(C) 2015爱思唯尔公司版权所有。
Polymeric nanoparticles (nano-paAPCs) modified with T-cell antigens and encapsulating immunostimulatory or immunoinhibitory factors may act as artificial antigen-presenting cells to circulating immune cells, improving the selective delivery of encapsulated drug or cytokine to antigen-specific T-cells. Paracrine delivery of encapsulated agents from these nanoparticles to adjacent cells facilitate sustained delivery lowering the overall administered dose, thus enhancing the overall drug efficacy while reducing toxicity of pleiotropic factors. Little is known mathematically regarding the local concentration of released agent that accumulates around a nanoparticle that is near or embeds in a cell. These concentration fields are calculated here in an attempt to understand paracrine efficacy of these nano-paAPC systems. The significant factor accumulation that can occur if the particles were to embed in the cell membrane may explain observed experimental data regarding enhanced T-cell activation and nanoparticle-mediated improvement in the drug delivery process to non-internalizing cellular targets. (C) 2015 Elsevier Inc. All rights reserved.