title: Cationic nanoparticles have superior transvascular flux into solid tumors: insights from a mathematical model.
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/m(2)) 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.
authors.affiliation: Department of Mechanical and Manufacturing Engineering, University of Cyprus, 1678, Nicosia, Cyprus. tstylian@ucy.ac.cy
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Stylianopoulos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Soteriou
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumura
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D002199:Capillary Permeability; D002412:Cations; D016503:Drug Delivery Systems; D008962:Models, Theoretical; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D009994:Osmolar Concentration; D055672:Static Electricity
chemical_list: D002412:Cations