TY - JOUR
T1 - Neovascularization-directed bionic eye drops for noninvasive renovation of age-related macular degeneration
AU - Ran, Meixin
AU - Deng, Yaxin
AU - Yan, Jiaqi
AU - Zhang, Anan
AU - Wei, Ying
AU - Li, Xiaowen
AU - He, Haibing
AU - Gou, Jingxin
AU - Yin, Tian
AU - Tang, Xing
AU - Kong, Jun
AU - Zhang, Han
AU - Zhang, Hongbo
AU - Zhang, Yu
N1 - Funding Information:
This work was supported by Shenyang Science and Technology Talent Support Program [RC210447], the National Natural Science Foundation of China (82172086, 81871472), National Key R&D Program of China [2020YFE0201700], Research Fellow (Grant No. 328933), Solution for Health Profile (336355), and InFLAMES Flagship (337531) grants from Academy of Finland. Finland China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture (No. 280M0052K1) Liaoning Revitalization Talents Program [XLYC1907111, XLYC1908031], Liaoning Province Doctoral Start-up Fund Program [2019-BS-226], Liaoning BaiQianWan Talents Program [(2020)78], Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University [ZQN2019004] and ‘Dual Service’ Program of University in Shenyang. Meixin Ran (CSC202207960005) and Jiaqi Yan (CSC202107960001) was sponsored by the China Scholarship Council.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/12/15
Y1 - 2022/12/15
N2 - The current treatment of wet age-related macular degeneration (wAMD) relies on monthly intravitreal or intravenously injection of vascular endothelial growth factor (VEGF) inhibitor or photodynamic (PDT) agents to inhibit choroidal neovascularization. However, traumatic local therapy and exogenous long-distance fundus drug delivery often lead to secondary eye damage, low treatment efficiency, and immunogenic inflammation. Herein, inspired by the natural neovascular targeting ability of endogenous low-density lipoproteins (LDL), a noninvasive bionic nano-eye-drop with enhanced ocular penetrability and lesion recognizability is developed for enabling the PDT treatment of wAMD. Verteporfin (VP) as a laser-induced PDT agent is protected inside the hydrophobic core of reconstituted LDL (rLDL) vectors. 5-carboxyfluorescein (FAM) conjugated ste-penetratin (PEN, a transmembrane peptide) is anchored on the surface of the rLDL carrier, which enabled the nanoparticles (PEN-rLDL-VP) to cross the blood-retina barrier to realizing visual therapy. Following instillation, PEN-rLDL-VP can effectively deliver VP into neovascular that overexpress LDL receptors, which can respond to laser-induced PDT. Only with a single dose of the eye-drop and laser-induced PDT, the VEGF and proinflammatory intercellular adhesion molecule-1 (ICAM-1) proteins are significantly down-regulated in vivo, which implicates the neovascular inhibition and inflammation alleviation. This study presents an attractive non-invasive strategy for the PDT of wAMD.
AB - The current treatment of wet age-related macular degeneration (wAMD) relies on monthly intravitreal or intravenously injection of vascular endothelial growth factor (VEGF) inhibitor or photodynamic (PDT) agents to inhibit choroidal neovascularization. However, traumatic local therapy and exogenous long-distance fundus drug delivery often lead to secondary eye damage, low treatment efficiency, and immunogenic inflammation. Herein, inspired by the natural neovascular targeting ability of endogenous low-density lipoproteins (LDL), a noninvasive bionic nano-eye-drop with enhanced ocular penetrability and lesion recognizability is developed for enabling the PDT treatment of wAMD. Verteporfin (VP) as a laser-induced PDT agent is protected inside the hydrophobic core of reconstituted LDL (rLDL) vectors. 5-carboxyfluorescein (FAM) conjugated ste-penetratin (PEN, a transmembrane peptide) is anchored on the surface of the rLDL carrier, which enabled the nanoparticles (PEN-rLDL-VP) to cross the blood-retina barrier to realizing visual therapy. Following instillation, PEN-rLDL-VP can effectively deliver VP into neovascular that overexpress LDL receptors, which can respond to laser-induced PDT. Only with a single dose of the eye-drop and laser-induced PDT, the VEGF and proinflammatory intercellular adhesion molecule-1 (ICAM-1) proteins are significantly down-regulated in vivo, which implicates the neovascular inhibition and inflammation alleviation. This study presents an attractive non-invasive strategy for the PDT of wAMD.
KW - Age-related macular degeneration
KW - Eye drops
KW - Low-density lipoproteins
KW - Penetratin
KW - Verteporfin
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U2 - 10.1016/j.cej.2022.138291
DO - 10.1016/j.cej.2022.138291
M3 - Article
AN - SCOPUS:85135023539
SN - 1385-8947
VL - 450
JO - Chemical Engineering Journal
JF - Chemical Engineering Journal
M1 - 138291
ER -