Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model
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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.
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- Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model
Annals of Biomedical Engineering
Volume 41, Issue 1 , pp 68-77
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Vascular permeability
- Electrostatic and hydrodynamic interactions
- Surface charge density
- Cancer therapy
- Industry Sectors
- Author Affiliations
- 1. Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus
- 2. Edwin L. Steele Laboratory for Tumor Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA