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Abstract
<p class="first" id="d7496776e172">Drugs with ideal pharmacokinetic profile require
long half-life but little organ accumulation.
Generally, PK and organ accumulation are contradictory factors: smaller size leads
to faster excretion and shorter half-lives and thus a lower tendency to reach targets;
larger size leads to longer circulation but stronger organ accumulation that leads
to toxicity. Organ accumulation has been reported to be size dependent due in large
part to engulfing by macrophages. However, publications on the size effect are inconsistent
because of complication by the effect of shape that varies from nanoparticle to nanoparticle.
Unique to RNA nanotechnology, size could be tuned without a change in shape, resulting
in a true size comparison. Here we investigated size effects using RNA squares of
identical shape but varying size and shape effects using RNA triangles, squares, and
pentagons of identical size but varying shape. We found that circulation time increased
with increasing RNA nanoparticle size from 5–25 nm, which is the common size range
of therapeutic RNA nanoparticles. Most particles were cleared from the body within
2 hr after systemic injection. Undetectable organ accumulation was found at any time
for 5 nm particles. For 20 nm particles, weak signal was found after 24 hr, while
accumulation in tumor was strongest during the entire study.
</p><p class="first" id="d7496776e175">Jasinski et al. explore the effects of RNA
nanoparticle size and shape on biodistribution
using RNA polygons. Animal imaging demonstrated a strong correlation between increased
size and increased circulation time. RNA nanoparticle size and shape are precisely
controlled, so different-size nanoparticles with identical shape could be studied.
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