Re-examining
the Size/Charge Paradigm: Differing in
Vivo Characteristics of Size- and Charge-Matched Mesoporous Silica
Nanoparticles
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Abstract
The
combination of nanoparticle (NP) size, charge, and surface
chemistry (e.g., extent of modification with polyethylene glycol (PEG))
is accepted as a key determinant of NP/cellular interactions. However,
the influence of spatial arrangement and accessibility of the charged
molecules on the NP surface <i>vis-à-vis</i> the
average surface charge (zeta (ζ) potential) is incompletely
understood. Here we demonstrate that two types of mesoporous silica
nanoparticles (MSNP) that are matched in terms of primary and hydrodynamic
particle size, shape, pore structure, colloidal stability, and ζ
potential, but differ in surface chemistry, <i>viz</i>.
the spatial arrangement and relative exposure of surface amines, have
profoundly different interactions with cells and tissues when evaluated <i>in vitro</i> and <i>in vivo</i>. While both particles
are ∼50 nm in diameter, PEGylated, and positively charged (ζ
= +40 mV), PEG-PEI (MSNPs modified with exposed polyamines), but not
PEG-NMe<sub>3</sub><sup>+</sup> (MSNP modified with distributed, obstructed
amines) rapidly bind serum proteins, diverse cells types <i>in
vitro</i>, and endothelial and white blood cells <i>in vivo</i> (ex ovo chick embryo model). This finding helps elucidate the relative
role of surface exposure of charged molecules vs ζ potential
in otherwise physicochemically matched MSNP and highlights protein
corona neutrality as an important design consideration when synthesizing
cationic NPs for biological applications