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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Impact of soft protein interactions on the excretion, extent of receptor occupancy and tumor accumulation of ultrasmall metal nanoparticles: a compartmental model simulation

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Author(s):
Sousa, Alioscka A.
Total Authors: 1
Document type: Journal article
Source: RSC ADVANCES; v. 9, n. 46, p. 26927-26941, AUG 27 2019.
Web of Science Citations: 1
Abstract

Ultrasmall metal nanoparticles (NPs) are next-generation nano-based platforms for in vivo disease diagnosis and treatment. Due to their small size below the kidney filtration threshold and marked resistance to nonspecific serum protein adsorption, ultrasmall NPs can be rapidly excreted through the kidneys and escape liver uptake. However, although ultrasmall particles may be deemed highly resistant to protein adsorption, the real extent of this resistance is not known. Here, a simple compartmental model simulation was therefore implemented to understand how NP behavior in vivo could be modulated by soft, transient NP-plasma protein interactions characterized by dissociation constants in the millimolar range. In Model 1, ultrasmall NPs functionalized with a targeting probe, plasma proteins and target receptors were assumed to co-exist within a single compartment. Simulations were performed to understand the synergistic effect of soft interactions, systemic clearance and NP size on receptor occupancy in the single compartment. The results revealed the existence of a narrow range of ultraweak affinities and optimal particle sizes leading to greater target occupancy. In Model 2, simulations were performed to understand the impact of soft interactions on NP accumulation into a peripheral (tumor) compartment. The results revealed that soft interactions - but not active targeting - enhanced tumor uptake levels when tumor accumulation was limited by `fast' plasma clearance and `slow' vascular extravasation. The simple model presented here provides a basic framework to quantitatively understand the blood and tumor pharmacokinetics of ultrasmall NPs under the influence of transient protein interactions. (AU)

FAPESP's process: 19/04372-6 - Interactions of ultrasmall gold nanoparticles with proteins and cells
Grantee:Alioscka Augusto Sousa
Support Opportunities: Regular Research Grants