posted on 2024-01-24, 14:03authored byReeddhi Ray, Santu Ghosh, Anupam Maity, Nikhil R. Jana
Nonendocytic
cell uptake of nanomaterials is challenging, which
requires specific surface chemistry and smaller particle size. Earlier
works have shown that an arginine-terminated nanoparticle of <10–20
nm size shows nonendocytic uptake via direct membrane penetration.
However, the roles of surface arginine density and the arginine-arginine
distance at the nanoparticle surface in controlling such nonendocytic
uptake mechanism is not yet explored. Here we show that a higher arginine
density at the nanoparticle surface with an arginine-arginine distance
of <3 nm is the most critical aspect for such nonendocytic uptake.
We have used quantum dot (QD)-based nanoparticles as a model for fluorescent
tracking inside cells and for quantitative estimation of cellular
uptake. We found that arginine-terminated nanoparticles of 10 nm size
can opt for the energy-dependent endocytosis pathway if the arginine-arginine
distance is >3 nm. In contrast, nanoparticles with <3 nm arginine-arginine
distance rapidly enter into the cell via the nonendocytic approach,
are freely available in the cytosol in large amounts to capture the
cellular adenosine triphosphate (ATP), generate oxidative stress,
and induce ATP-deficient cellular autophagy. This work shows that
arginine-arginine distance at the nanoparticle surface is another
fundamental parameter, along with the particle size, for the nonendocytic
cell uptake of foreign materials and to control intracellular activity.
This approach may be utilized in designing nanoprobes and nanocarriers
with more efficient biomedical performances.