A Ferroptosis Nano Inhhibitor To Alleviate Diabetic Osteoporosis

The objective of our study was to synthesize and validate a ferroptosis-suppressing nanoparticle using tFNA that would deliver a natural product, specifically icariin(ICA), to alleviate the diabetic Osteoporosis(DOP). Synthesis and characterization of tFNA@ICA; Isolation and culture of BMSCs; BMSCs uptake of icariin and tFNA@ICA; AGEs-induced ferroptosis and osteogenic differentiation of BMSCs; ALP and alizarin red staining; ROS level detection assay; FerroOrange staining; TEM; Western blot; IF; Animal experiments; Micro-CT analyses; Histological analysis; tFNAs@ICA promoted osteogenic differentiation of BMSCs in vitro, even in an AGEs-rich environment. This phenomenon seemed to be associated with resistance to oxidative stress, lipid peroxidation and ferroptosis. tFNAs@ICA alleviated the systemic microenvironment of diabetes in vivo, reducing serum AGEs levels, mitigating progressive pancreatic damage, as well as alleviating insulin resistance and hepatic steatosis. Meanwhile, tFNAs@ICA prevented DOP and maintained trabecular number and separation. Ferroptosis, initially discovered in 2012, is characterized as an iron-dependent form of cell death and has been strongly associated with diabetes and its complications. The primary strategy for managing DOP is to alleviate the systemic microenvironment of diabetes.In this study, we developed a ferroptosis-suppressing tFNA nanoparticles to deliver icariin to BMSCs treated with AGEs and to DOP model mice, to evaluate tFNA@ICA application as a potential treatment option of diabetes and DOP. Targeting ferroptosis to alleviate the systemic microenvironment of diabetes as well as diabetic osteoporosis is a promising therapeutic approach.