Original Paper

Computational Mechanics

, Volume 53, Issue 3, pp 511-537

Multiscale modeling and uncertainty quantification in nanoparticle-mediated drug/gene delivery

  • Ying LiAffiliated withDepartment of Mechanical Engineering, Northwestern University
  • , Wylie StrobergAffiliated withTheoretical & Applied Mechanics, Northwestern University
  • , Tae-Rin LeeAffiliated withDepartment of Mechanical Engineering, Northwestern UniversityDepartment of Translational Imaging, The Methodist Hospital Research Institute
  • , Han Sung KimAffiliated withDepartment of Mechanical Engineering, Northwestern University
  • , Han ManAffiliated withDepartment of Mechanical Engineering, Northwestern University
  • , Dean HoAffiliated withDepartment of Mechanical Engineering, Northwestern UniversityDepartment of Biomedical Engineering, Institute for Bionanotechnology in Medicine (IBNAM), Robert H. Lurie Comprehensive Cancer Center, Northwestern UniversityDivision of Oral Biology and Medicine, Division of Advanced Prosthodontics, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, UCLA Department of Bioengineering, Jonsson Comprehensive Cancer Center, California NanoSystems Institute
  • , Paolo DecuzziAffiliated withDepartment of Translational Imaging, The Methodist Hospital Research Institute
  • , Wing Kam LiuAffiliated withDepartment of Mechanical Engineering, Northwestern UniversityDistinguished Scientists Program Committee, King Abdulaziz University (KAU) Email author 

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Abstract

Nanoparticle (NP)-mediated drug/gene delivery involves phenomena at broad range spatial and temporal scales. The interplay between these phenomena makes the NP-mediated drug/gene delivery process very complex. In this paper, we have identified four key steps in the NP-mediated drug/gene delivery: (i) design and synthesis of delivery vehicle/platform; (ii) microcirculation of drug carriers (NPs) in the blood flow; (iii) adhesion of NPs to vessel wall during the microcirculation and (iv) endocytosis and exocytosis of NPs. To elucidate the underlying physical mechanisms behind these four key steps, we have developed a multiscale computational framework, by combining all-atomistic simulation, coarse-grained molecular dynamics and the immersed molecular electrokinetic finite element method (IMEFEM). The multiscale computational framework has been demonstrated to successfully capture the binding between nanodiamond, polyethylenimine and small inference RNA, margination of NP in the microcirculation, adhesion of NP to vessel wall under shear flow, as well as the receptor-mediated endocytosis of NPs. Moreover, the uncertainties in the microcirculation of NPs has also been quantified through IMEFEM with a Bayesian updating algorithm. The paper ends with a critical discussion of future opportunities and key challenges in the multiscale modeling of NP-mediated drug/gene delivery. The present multiscale modeling framework can help us to optimize and design more efficient drug carriers in the future.

Keywords

Drug delivery Multiscale modeling Coarse-grained molecular dynamics Fluid-structure interaction Immersed molecular electrokinetic finite element Molecular mean-field theory