TY - JOUR

T1 - Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence

AU - Dong, J.

AU - Wang, Q.

AU - Gu, T.

AU - Liu, G.

AU - Petrov, Y.V.

AU - Baulin, V.E.

AU - Tsivadze, A.Yu

AU - Jia, D.

AU - Zhou, Y.

AU - Yuan, H.

AU - Li, B.

N1 - Export Date: 21 March 2024 CODEN: JCISA Адрес для корреспонденции: Yuan, H.; Department of Ophthalmology, China; эл. почта: yuanhp2013@126.com Химические вещества/CAS: carbon, 7440-44-0; chitosan, 9012-76-4; hydroxyl radical, 3352-57-6; protein p21, 85306-28-1; sirolimus, 53123-88-9 Сведения о финансировании: GA20C008 Сведения о финансировании: 2022ZX02C24 Сведения о финансировании: SWZ-ZD202103 Сведения о финансировании: 2022TS21 Сведения о финансировании: National Natural Science Foundation of China, NSFC, 51972086, 52061135204, 82070956 Сведения о финансировании: Ministry of Education and Science of the Russian Federation, Minobrnauka, 075-15-2022-1114 Сведения о финансировании: Russian Science Foundation, RSF, 21-43-00020 Текст о финансировании 1: This work was financially supported by Interdisciplinary Research Foundation of HIT ( IR2021105 ), National Natural Science Foundation of China ( 52061135204 , 51972086, 82070956 ), Heilongjiang Provincial Key R&D projects ( 2022ZX02C24 ), Ministry of Science and Higher Education of the Russian Federation ( 075-15-2022-1114 ), Key Laboratory of Bio-based Material Science & Technology (Northeast Forestry University) Ministry of Education ( SWZ-ZD202103 ), State Key Laboratory of Urban Water Resource and Environment of Harbin Institute of Technology ( 2022TS21 ) and Russian Science Foundation ( 21-43-00020 ), Applied Technology Research and Development Program of Heilongjiang Provincial Science and Technology Department (GA20C008).

PY - 2024/4/1

Y1 - 2024/4/1

N2 - 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. © 2024 Elsevier Inc.

AB - 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. © 2024 Elsevier Inc.

KW - Carbon dots

KW - Cell senescence

KW - Chitosan

KW - Rapamycin

KW - ROS

KW - Target-oriented synthesis

KW - Antibiotics

KW - Carbon

KW - Carbonization

KW - Controlled drug delivery

KW - Cytology

KW - Diseases

KW - Endothelial cells

KW - Mammals

KW - Oxidative stress

KW - Solubility

KW - Cell senescences

KW - Functionalized

KW - Mammalian target

KW - Reactive oxygen species

KW - Scavenging ability

KW - Target of rapamycin

KW - Target oriented

KW - Free radicals

KW - carbon

KW - chitosan

KW - hydroxyl radical

KW - mammalian target of rapamycin

KW - protein p16

KW - protein p21

KW - protein p53

KW - reactive oxygen metabolite

KW - sirolimus

KW - Article

KW - carbonization

KW - cell aging

KW - human

KW - human cell

KW - IC50

KW - mTOR signaling

KW - oxidative stress

KW - polymerization

KW - signal transduction

KW - synthesis

KW - umbilical vein endothelial cell

KW - vascularization

KW - water solubility

KW - article

KW - atherosclerosis

KW - controlled study

KW - nonhuman

KW - pharmacology

UR - https://www.mendeley.com/catalogue/93e81505-146c-3ba1-8bfe-d70c631ab8e1/

U2 - 10.1016/j.jcis.2024.01.032

DO - 10.1016/j.jcis.2024.01.032

M3 - статья

VL - 660

SP - 534

EP - 544

JO - Journal of Colloid and Interface Science

JF - Journal of Colloid and Interface Science

SN - 0021-9797

ER -