Ntarakas Nikolaos, Lah Maša, Svenšek Daniel, Potisk Tilen, Praprotnik Matej
Laboratory for Molecular Modeling, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana, Slovenia.
ACS Appl Nano Mater. 2025 Aug 4;8(32):16053-16070. doi: 10.1021/acsanm.5c02783. eCollection 2025 Aug 15.
Ultrasound-guided drug and gene delivery (usdg) enables controlled and spatially precise delivery of drugs and macromolecules, encapsulated in microbubbles (embs) and nanoscale gas vesicles (gvs), to target areas such as cancer tumors. It is a noninvasive, high precision, low toxicity process with drastically reduced drug dosage. Rheological and acoustic properties of gvs and embs critically affect the outcome of usdg and imaging. Detailed understanding and modeling of their physical properties is thus essential for ultrasound-mediated therapeutic applications. State-of-the-art continuum models of shelled bodies cannot incorporate critical details such as varying thickness of the encapsulating shell or specific interactions between its constituents and interior or exterior solvents. Such modeling approaches also do not allow for detailed modeling of chemical surface functionalizations, which are crucial for tuning the gv-blood interactions. We develop a general particle-based modeling framework for encapsulated bodies that accurately captures elastic and rheological properties of gvs and embs at the mesoscopic and nanoscale levels. We use dissipative particle dynamics to model the solvent, the gaseous phase in the capsid, and the triangulated surfaces of immersed objects. Their elastic behavior is studied and validated through stretching and buckling simulations, eigenmode analysis, shear flow simulations, and comparison of predicted gv buckling pressure with published experimental data. The presented modeling approach paves the way for large-scale simulations of nanoscale and microscale encapsulated bodies of different shapes and local anisotropy, capturing their dynamics, interactions, and collective behavior.
超声引导下的药物和基因递送（USDG）能够将包裹在微泡（MBs）和纳米级气体囊泡（GVs）中的药物和大分子可控且在空间上精确地递送至癌症肿瘤等靶区域。这是一种非侵入性、高精度、低毒性的过程，能大幅降低药物剂量。GVs和MBs的流变学和声学特性对USDG及成像结果有着至关重要的影响。因此，详细了解并模拟它们的物理特性对于超声介导的治疗应用至关重要。现有的带壳物体连续介质模型无法纳入诸如封装壳厚度变化或其成分与内部或外部溶剂之间特定相互作用等关键细节。此类建模方法也无法对化学表面功能化进行详细建模，而化学表面功能化对于调节GV与血液的相互作用至关重要。我们为封装物体开发了一个通用的基于粒子的建模框架，该框架能在介观和纳米尺度准确捕捉GVs和MBs的弹性和流变学特性。我们使用耗散粒子动力学来模拟溶剂、衣壳内的气相以及浸入物体的三角化表面。通过拉伸和屈曲模拟、本征模分析、剪切流模拟以及将预测的GV屈曲压力与已发表的实验数据进行比较，对它们的弹性行为进行了研究和验证。所提出的建模方法为大规模模拟不同形状和局部各向异性的纳米级和微米级封装物体铺平了道路，能够捕捉它们的动力学、相互作用和集体行为。
