Type 2 diabetes (T2D) results from the cells’
insulin resistance,
and to date, insulin therapy and diabetes medications targeting glycemic
management have failed to reverse the increase in T2D prevalence.
Restoring liver functions to improve hepatic insulin resistance by
reducing oxidative stress is a potential strategy for T2D treatment.
Herein, the liver-targeted biodegradable silica nanoshells embedded
with platinum nanoparticles (Pt-SiO2) are designed as reactive
oxygen species (ROS) nanoscavengers and functional hollow nanocarriers.
Then, 2,4-dinitrophenol-methyl ether (DNPME, mitochondrial uncoupler)
is loaded inside Pt-SiO2, followed by coating a lipid bilayer
(D@Pt-SiO2@L) for long-term effective ROS removal (platinum
nanoparticles scavenge overproduced ROS, while DNPME inhibits ROS
production) in the liver tissue of T2D models. It is found that D@Pt-SiO2@L reverses elevated oxidative stress, insulin resistance,
and impaired glucose consumption in vitro, and significantly
improves hepatic steatosis and antioxidant capacity in diabetic mice
models induced by a high-fat diet and streptozotocin. Moreover, intravenous
administration of D@Pt-SiO2@L indicates therapeutic effects
on hyperlipidemia, insulin resistance, hyperglycemia, and diabetic
nephropathy, which provides a promising approach for T2D treatment
by reversing hepatic insulin resistance through long-term ROS scavenging.