Design
and development of silica nanoparticles (SiO<sub>2</sub> NPs) with
a controlled degradation profile promises effective drug
delivery with a predetermined carrier elimination profile. In this
research, we fabricated a series of redox-responsive polysulfide-based
biodegradable SiO<sub>2</sub> NPs with low polydispersity and with
variations in size (average diameters of 58 ± 7, 108 ± 11,
110 ± 9, 124 ± 9, and 332 ± 6 nm), porosity, and composition
(disulfide vs tetrasulfide bonds). The degradation kinetics of the
nanoparticles was analyzed in the presence of 8 mM glutathione (GSH),
mimicking the intracellular reducing condition. Results indicate that
porosity and core composition play the predominant roles in the degradation
rate of these nanoparticles. The 108 nm mesoporous disulfide-based
nanoparticles showed the highest degradation rate among all the synthesized
nanoparticles. Transmission electron microscopy (TEM) reveals that
nonporous nanoparticles undergo surface erosion, while porous nanoparticles
undergo both surface and bulk erosion under reducing environment.
The cytotoxicity of these nanoparticles in RAW 264.7 macrophages was
evaluated. Results show that all these nanoparticles with the IC<sub>50</sub> values ranging from 233 ± 42 to 705 ± 17 μg
mL<sup>–1</sup> do not have cytotoxic effect in macrophages
at concentrations less than 125 μg mL<sup>–1</sup>. The
degradation products of these nanoparticles collected within 15 days
did not show cytotoxicity in the same macrophage cell line after 24
h of incubation. <i>In vitro</i> doxorubicin (DOX) release
was examined in 108 nm mesoporous disulfide-based nanoparticles in
the absence and presence of 8 mM GSH. It was shown that drug release
depends on intracellular reducing conditions. Due to their ease of
synthesis and scale up, robust structure, and the ability to control
size, composition, release, and elimination, biodegradable SiO<sub>2</sub> NPs provide an alternative platform for delivery of bioactive
and imaging agents