Acid-responsive aggregated carrot-derived nanoantioxidants alleviate oxidative stress and restore osteoblast activity

Excessive generation of reactive oxygen species is a hallmark of the osteoporotic bone microenvironment, which leads to the damage of mitochondrial function and the deactivation of osteoblasts. Fruits and vegetables are rich sources of antioxidants, which play a key role in scavenging free radicals and maintaining the body's homeostasis. Herein, we have developed a type of vesicle coming from carrots as nanoantioxidants to counteract oxidative stress and restore the vitality of osteoblasts for reversing osteoporosis. Nanovesicles are derived from carrot juice using a straightforward extrusion method, resulting in stable membrane structures containing various lipids and homologous active phytochemicals. Nanovesicles can maintain stable structures under normal physiological conditions (pH 7.4) and transform into aggregates in response to the acidic extracellular pH of osteoporosis (pH 4.0). As anticipated, nanovesicles can passively target and aggregate to osteoporotic bone, ease oxidative stress, restore mitochondrial function, promote osteoblastogenesis, and reduce bone loss in osteoporotic mice. This work presents the first demonstration of nanovesicles derived from carrots as novel nanoantioxidants to realize the long-awaited osteogenesis, contributing to the exploration of a brand-new idea for reversing osteoporosis.