Biodegradable Hollow Nanoscavengers Restore Liver Functions to Reverse Insulin Resistance in Type 2 Diabetes.
Zhibin ZhangDongtao ZhouXiaowei LuanXuyuan WangZhenxing ZhuWen LuoJingjing YangShaochun TangYujun SongPublished in: ACS nano (2023)
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-SiO 2 ) 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-SiO 2 , followed by coating a lipid bilayer (D@Pt-SiO 2 @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-SiO 2 @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-SiO 2 @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.
Keyphrases
- insulin resistance
- high fat diet
- type diabetes
- reactive oxygen species
- glycemic control
- oxidative stress
- dna damage
- adipose tissue
- drug delivery
- cell death
- high fat diet induced
- diabetic nephropathy
- polycystic ovary syndrome
- skeletal muscle
- metabolic syndrome
- cancer therapy
- induced apoptosis
- diabetic rats
- blood glucose
- cardiovascular disease
- magnetic nanoparticles
- cell cycle arrest
- ischemia reperfusion injury
- risk factors
- fatty acid
- high dose
- combination therapy
- cell proliferation
- mass spectrometry
- metal organic framework
- low dose
- bone marrow