Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Nanozyme Medical Center, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
J Control Release. 2022 Oct;350:271-283. doi: 10.1016/j.jconrel.2022.08.026. Epub 2022 Aug 25.
Retinal neovascularization is typically accompanied by hypoxia-induced oxidative injury in the vascular system. This study developed an ultrasmall (6-8 nm) platinum (Pt) nanozyme loaded mitochondria-targeted liposome (Pt@MitoLipo) to alleviate hypoxia and eliminate excess reactive oxygen species (ROS) for effective retinal neovascularization disease therapy. Pt nanozymes possess superoxide dismutase (SOD) and catalase (CAT) cascade enzyme-like activities, which convert cytotoxic O and HO into nontoxic HO and O. Triphenylphosphonium (TPP)-conjugated liposomes were coated on the surface of Pt nanozymes to increase their biocompatibility and help them penetrate the cell membrane, escape from the lysosomal barrier, and target mitochondria, thus achieving precise scavenging of mitochondrial O and relief from hypoxia. Using an oxygen-induced retinopathy (OIR) mouse model, we demonstrated that Pt@MitoLipo nanozymes significantly suppressed hypoxia-induced abnormal neovascularization and facilitated avascular normalization of the retina in vivo without any noticeable toxicity. This study provides a promising way to break through cellular barriers and target scavenging mitochondrial O and illustrates the potential of ROS-scavenging and hypoxia relief in retinal neovascularization disease therapy.
视网膜新生血管形成通常伴随着血管系统中缺氧诱导的氧化损伤。本研究开发了一种超小（6-8nm）载铂（Pt）纳米酶的线粒体靶向脂质体（Pt@MitoLipo），以减轻缺氧并消除过量的活性氧（ROS），从而有效治疗视网膜新生血管疾病。Pt 纳米酶具有超氧化物歧化酶（SOD）和过氧化氢酶（CAT）级联酶样活性，可将细胞毒性 O 和 HO 转化为无毒的 HO 和 O。三苯基膦（TPP）修饰的脂质体被包裹在 Pt 纳米酶表面，以提高其生物相容性并帮助其穿透细胞膜，逃避溶酶体屏障，并靶向线粒体，从而实现对线粒体 O 的精确清除和缓解缺氧。利用氧诱导的视网膜病变（OIR）小鼠模型，我们证明了 Pt@MitoLipo 纳米酶显著抑制了缺氧诱导的异常新生血管形成，并促进了体内视网膜无血管的正常化，而没有任何明显的毒性。这项研究为突破细胞屏障并靶向清除线粒体 O 提供了一种有前途的方法，并说明了 ROS 清除和缓解缺氧在视网膜新生血管疾病治疗中的潜力。
