Attenuating Uncontrolled Inflammation by Radical Trapping Chiral Polymer Micelles.
Yao LiJie WangYaru LiJiajia LuoFang LiuTiantian ChenYuting JiHong YangZheng WangYanjun ZhaoPublished in: ACS nano (2023)
As a clinical unmet need, uncontrolled inflammation is characterized by the crosstalk between oxidative stress and an inflammatory response. Ferroptotic cell death plays an essential role in uncontrolled inflammation. Hence ferroptosis inhibition is capable of managing hyper-inflammation, but the small molecular inhibitors show poor residence in cell membranes. The plasma membrane is the major site of lipid peroxidation that is the key event of ferroptosis. To address such a challenge, chiral radical trapping polymers were engineered by mimicking the structure of the cell membrane with imbedded helical proteins. The polymers were tailored to show an α-helix conformation that enabled increased hydrophobicity, prolonged membrane retention, and enhanced lipid radical trapping. The chiral polymers are amphiphilic, and the self-assembled micelles exhibited an extended blood circulation. At the lipopolysaccharide-induced macrophage and mice models, chiral polymer micelles effectively suppressed ferroptosis and repressed inflammatory cytokines. The current work provides an innovative means for attenuating uncontrolled inflammation by anti-ferroptotic polymer micelles.
Keyphrases
- oxidative stress
- cell death
- inflammatory response
- lipopolysaccharide induced
- drug delivery
- cancer therapy
- drug release
- diabetic rats
- ionic liquid
- capillary electrophoresis
- ischemia reperfusion injury
- toll like receptor
- stem cells
- adipose tissue
- dna damage
- bone marrow
- mass spectrometry
- lps induced
- transcription factor
- cell therapy