Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence

Rapa functionalized carbon dots (Rapa-CDs) were target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization technology. Rapa-CDs has a high synthetic yield of 63%. The solubility of Rapa-CDs with 9.41 g is improved 3.6×104 times higher than that of Rapa (2.6×10-4 g). Rapa-CDs show the ability to scavenge ROS, and suppress cell senescence via anti-oxidative stress and mTOR. [Display omitted] •Rapa-CDs with synthetic yield of 63% were target-oriented synthesized.•Rapa-CDs increase Rapa solubility by 3.6 × 104 times and show ROS scavenging ability.•Rapa-CDs suppress vascular cell senescence via anti-oxidative stress and mTOR. Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.