Junmei Tang,Sihao Liu,Yuemei Han,Rui Wang,Jiayi Xia,Hao Chen,Quankui Lin
Posterior capsular opacification (PCO) is an emerging complication in cataract phacoemulsification and intraocular lens (IOL) implantation surgery, mainly stemming from the adhesion, proliferation, and trans-differentiation of the post-surgery residual lens epithelial cells (LECs). Previous investigations have shown that an anti-proliferative drug eluting coating on the IOL surface provides an effective way to inhibit PCO. However, due to the undesirable elution of the anti-proliferative drug, the safety of such modification is one of the important issues to be solved. In this investigation, photodynamic coating was introduced into IOL surface modification. The photosensitizer chlorin e6 grafted α-cyclodextrin (α-CD-Ce6) was synthesized and self-assembled onto the poly(poly(ethylene glycol) methacrylate) (PPEGMA) brush established IOL surface via the supramolecular interaction between α-CD and poly(ethylene glycol) chains. The results of investigation into its optical properties, including transmittance, refractive index, and surface morphology, showed no obvious alterations after photodynamic coating modification on the IOL surface. The in vitro LEC behaviour investigation optimized the photodynamic therapy parameters when light illumination was used for the cell elimination on the photodynamic coating modified IOL. The results have also shown that this functional coating modification effectively eliminates the cells on the surface of the IOL material when treated with light illumination, whereas it keeps excellent cytocompatibility in the absence of light illumination. The investigation of the cell elimination mechanism shows that this kind of functional coating eliminates the adherent cells by ROS induced apoptosis. The in vivo implantation result confirms the excellent PCO inhibition effect, as well as their safety and biocompatibility to the surrounding tissues. As a result, the proposed photodynamic coating provides a safer and effective alternative of IOL modification for preventing PCO.
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.
危险品化学品经营许可证（带存储）