Nanoparticle (NP)-based imaging and drug delivery systems for systemic (e.g. intravenous) therapeutic and diagnostic applications are inherently a complex integration of biology and engineering. A broad range of length and time scales are essential to hydrodynamic and microscopic molecular interactions mediating NP (drug nanocarriers, imaging agents) motion in blood flow, cell binding/uptake, and tissue accumulation. A computational model of time-dependent tissue delivery, providing in silico prediction of organ-specific accumulation of NPs, can be leveraged in NP design and clinical applications. In this article, we provide the current state-of-the-art and future outlook for the development of predictive models for NP transport, targeting, and distribution through the integration of new computational schemes rooted in statistical mechanics and transport. The resulting multiscale model will comprehensively incorporate: (i) hydrodynamic interactions in the vascular scales relevant to NP margination; (ii) physical and mechanical forces defining cellular and tissue architecture and epitope accessibility mediating NP adhesion; and (iii) subcellular and paracellular interactions including molecular-level targeting impacting NP uptake.

中文翻译：

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用于纳米颗粒靶向药物递送的蛋白质膜相互作用的多尺度建模。

用于全身（例如静脉内）治疗和诊断应用的基于纳米粒子 (NP) 的成像和药物递送系统本质上是生物学和工程学的复杂整合。广泛的长度和时间尺度对于介导血流中 NP（药物纳米载体、显像剂）运动、细胞结合/摄取和组织积累的流体动力学和微观分子相互作用至关重要。时间依赖性组织递送的计算模型，提供 NPs 器官特异性积累的计算机预测，可用于 NP 设计和临床应用。在本文中，我们为 NP 运输、靶向、通过整合基于统计力学和传输的新计算方案进行分配。由此产生的多尺度模型将全面纳入：（i）与 NP 边缘相关的血管尺度中的流体动力学相互作用；(ii) 定义细胞和组织结构以及介导 NP 粘附的表位可及性的物理和机械力；(iii) 亚细胞和细胞旁相互作用，包括影响 NP 摄取的分子水平靶向。