Computational Mechanics

, Volume 53, Issue 3, pp 511–537 | Cite as

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

  • Ying Li
  • Wylie Stroberg
  • Tae-Rin Lee
  • Han Sung Kim
  • Han Man
  • Dean Ho
  • Paolo Decuzzi
  • Wing Kam Liu
Original Paper

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 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ying Li
    • 1
  • Wylie Stroberg
    • 3
  • Tae-Rin Lee
    • 1
    • 6
  • Han Sung Kim
    • 1
  • Han Man
    • 1
  • Dean Ho
    • 1
    • 4
    • 5
  • Paolo Decuzzi
    • 6
  • Wing Kam Liu
    • 1
    • 2
  1. 1.Department of Mechanical EngineeringNorthwestern UniversityEvanstonUSA
  2. 2.Distinguished Scientists Program CommitteeKing Abdulaziz University (KAU)JeddahSaudi Arabia
  3. 3.Theoretical & Applied MechanicsNorthwestern UniversityEvanstonUSA
  4. 4.Department of Biomedical Engineering, Institute for Bionanotechnology in Medicine (IBNAM), Robert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicagoUSA
  5. 5.Division 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 BioengineeringJonsson Comprehensive Cancer Center, California NanoSystems InstituteLos AngelesUSA
  6. 6.Department of Translational ImagingThe Methodist Hospital Research InstituteHoustonUSA

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