■眼部疾病的药物治疗受到多种保护机制的限制,可以使用精心设计的药物递送系统进行改进。介孔二氧化硅纳米粒子(MSNs)作为眼病治疗药物的载体已在许多研究中使用。然而,目前尚无针对眼生物安全性的研究.考虑到含有四硫磺键的MSN具有独特的优势,并在药物递送系统中引起了越来越多的关注,在其作为眼科药物载体的广泛应用之前,有必要探索四苏夫键的眼部生物安全性。
■在这项研究中,制备并表征了具有不同四巯基键含量的中空介孔二氧化硅纳米粒子(HMSNs)。HMSN-E的眼部生物安全性在体外评估了三种选择的眼部细胞系,包括角膜上皮细胞,晶状体上皮细胞和视网膜内皮细胞(HREC),并在体内使用局部滴眼液和玻璃体内注射。
■在细胞实验中,HMSNs引起明显的S含量依赖性细胞毒性作用。HMSNs具有最高的四硫磺键含量(HMSN-E),在所有HMSN中显示出最高的细胞毒性,HREC是最容易受到HMSN-E攻击的细胞结果表明,HMSN-E可以与细胞内GSH反应生成H2S并降低细胞内GSH浓度。用HMSN-E治疗HREC增加细胞内ROS,线粒体膜电位降低,并在G1/S检查点诱导细胞周期停滞,最终引起HREC细胞凋亡和坏死。HMSN-E局部滴眼液可引起角膜损伤。玻璃体内注射HMSN-E可引起玻璃体和神经节细胞层炎症,导致玻璃体混浊和视网膜异常。
■在HMSN中掺入四苏富键可对眼部组织产生毒性作用。因此,当介孔二氧化硅纳米载体被设计用于眼科药物时,应考虑四苏富键的眼部毒性。
UNASSIGNED: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers.
UNASSIGNED: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections.
UNASSIGNED: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities.
UNASSIGNED: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.