Huang Yanjuan, Zhang Tao, Wei Qin, Zeng Zishan, Gong Yujun, Xu Xiaoyu, Chen Meixu, Zhao Chunshun
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Asian J Pharm Sci. 2022 Nov;17(6):838-854. doi: 10.1016/j.ajps.2022.10.004. Epub 2022 Nov 5.
Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a "NIR-triggered ROS storage" intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.
后囊膜混浊（PCO）是白内障术后视力丧失的主要原因，主要由术后残留晶状体上皮细胞（LECs）的黏附、增殖和转分化引起。几十年来，有效的PCO预防对眼科医生和研究人员来说仍然是一个巨大的挑战。在此，我们基于囊袋张力环（CTR）开发了一种“近红外触发ROS储存”眼内植入物（CTR-Py-PpIX），其同时与光敏剂原卟啉IX（PpIX）和储能2-吡啶酮衍生物（Py）相连，以确保为杀死LECs产生瞬时且可持续的ROS，旨在实现更高效、更安全的光动力疗法（PDT）以有效预防PCO。将硅烷化的PpIX-Si和Py-Si共价缀合到等离子体活化的CTR表面以获得CTR-Py-PpIX。结果表明，CTR-Py-PpIX具有PDT和电池的双重功能，其中PpIX在照射下可在细胞外产生活性氧，一部分通过诱导细胞膜脂质过氧化（LPO）直接抑制LECs。同时，照射去除后，储存在Py中的过量ROS可持续释放以放大LPO水平。最终，在温和的照射条件下，囊袋内LECs的增殖被完全抑制，实现了可持续且可控的PDT效应，以有效预防PCO且具有良好的生物相容性。这种近红外触发ROS储存眼内植入物将为长期预防PCO提供一种更高效、更安全的方法。
