Self-Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments

被引：0

作者：

Zhou, Xuezhi ^{[1
,2
,3
]}

Rong, Rong ^{[1
,2
,3
]}

Liang, Ganghao ^{[4
,5
]}

Wu, Yukun ^{[1
,2
,3
]}

Xu, Chun ^{[6
]}

Xiao, Haihua ^{[4
,5
]}

Ji, Dan ^{[1
,2
,3
]}

Xia, Xiaobo ^{[1
,2
,3
]}

机构：

[1] Cent South Univ, Xiangya Hosp, Dept Ophthalmol, Changsha 410008, Hunan, Peoples R China

[2] Hunan Key Lab Ophthalmol, Changsha 410008, Hunan, Peoples R China

[3] Cent South Univ, Natl Clin Res Ctr Geriatr Dis, Changsha 410008, Hunan, Peoples R China

[4] Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, State Key Lab Polymer Phys, Beijing 100190, Peoples R China

[5] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[6] Univ Queensland, Sch Dent, Brisbane 4006, Australia

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 41期

基金：

中国国家自然科学基金;

关键词：

apoptosis; axonal damage; glaucoma; HOLN-NPs; retina ganglion cells;

D O I：

10.1002/advs.202407043

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS-responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self-assembled into nanoparticles (uhOLN-NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN-NPs to form nanoparticles with hypoxic and ROS responses (HOLN-NPs). Under hypoxia in RGCs, the azo bond of HOLN-NPs breaks and releases uhOLN-NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano-prodrug. The released nicotinamide and oleic acid co-scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN-NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN-NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN-NPs provide a new therapeutic approach for patients with neurodegenerative disease. A dual hypoxia and ROS-responsive nano drug system for Nico and OA (HOLN-NPs) can be injected into the eye to protect RGCs. HOLN-NPs show promising potential in protecting RGCs from apoptosis and axonal damage, providing a new therapeutic approach for patients with neurodegenerative disease. image

引用

页数：18