Acute lung injury (ALI) and acute respiratory distress
syndrome
are triggered by complicated molecular mechanisms, which are the prime
causes of high mortality in critical patients. Recent research suggests
that the release of high levels of IL-1β and IL-18, resulting
from pyroptosis, plays a pivotal role in causing cytokine storms that
lead to severe respiratory damage. DNA nanostructures possess desirable
properties, such as biocompatibility, programmability, biodegradability,
and nontoxicity, making them suitable for use as drug delivery vehicles.
In this study, it has been found that the DNA nanoprism acts as a
carrier to deliver buformin, which serves as not only a mediator for
DNA assembly but also a drug that inhibits NOD-like receptor family
pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. To enhance
the therapeutic effect of buformin, six p65 siRNA molecules are loaded
onto the DNA nanoprism. Both buformin and p65 siRNA demonstrated remarkable
inhibition of NLRP3-mediated pyroptosis. Furthermore, the synergistic
effect of the p65 siRNA-loaded buformin/DNA nanoprism in reducing
inflammation levels by inhibiting pyroptosis was investigated in both
an in vitro model of macrophage cell pyroptosis and an in vivo model
of ALI mice. In conclusion, this DNA nanoplatform has the potential
to change the future treatment of ALI as it carries two therapeutic
agents simultaneously, resulting in synergistic therapeutic effects.
This proposed approach offers new strategies that could enhance the
overall effectiveness of the ALI treatment.