Annals of Biomedical Engineering

, Volume 41, Issue 1, pp 68–77

Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model

Article

DOI: 10.1007/s10439-012-0630-4

Cite this article as:
Stylianopoulos, T., Soteriou, K., Fukumura, D. et al. Ann Biomed Eng (2013) 41: 68. doi:10.1007/s10439-012-0630-4

Abstract

Despite their great promise, only a few nanoparticle formulations have been approved for clinical use in oncology. The failure of nano-scale drugs to enhance cancer therapy is in large part due to inefficient delivery. To overcome this outstanding problem, a better understanding of how the physical properties (i.e., size, surface chemistry, and shape) of nanoparticles affect their transvascular transport in tumors is required. In this study, we developed a mathematical model for nanoparticle delivery to solid tumors taking into account electrostatic interactions between the particles and the negatively-charged pores of the vessel wall. The model predictions suggest that electrostatic repulsion has a minor effect on the transvascular transport of nanoparticles. On the contrary, electrostatic attraction, caused even by small cationic charges (surface charge density less than 3 × 10−3 C/m2) can lead to a twofold or more increase in the transvascular flux of nanoparticles into the tumor interstitial space. Importantly, for every nanoparticle size, there is a value of charge density above which a steep increase in transvascular transport is predicted. Our model provides important guidelines for the optimal design of nanoparticle formulation for delivery to solid tumors.

Keywords

Vascular permeabilityElectrostatic and hydrodynamic interactionsSurface charge densityNanomedicineCancer therapy

Supplementary material

10439_2012_630_MOESM1_ESM.pdf (287 kb)
Supplementary material 1 (PDF 287 kb)

Copyright information

© Biomedical Engineering Society 2012

Authors and Affiliations

  1. 1.Department of Mechanical and Manufacturing EngineeringUniversity of CyprusNicosiaCyprus
  2. 2.Edwin L. Steele Laboratory for Tumor BiologyMassachusetts General Hospital, Harvard Medical SchoolBostonUSA