“NIR-triggered ROS storage” photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Abstract

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.