Exploring the Potential of Nanoporous Materials for Advancing Ophthalmic Treatments

Wu, Kevin Y.; Brister, Danielle; Bélanger, Paul; Tran, Simon D.

doi:10.3390/ijms242115599

Cited by 2 publications

(1 citation statement)

References 78 publications

(95 reference statements)

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“… 32–37 Although MSNs have gained increasing interest in ocular drug delivery systems, limited ocular biosafety research poses potential concerns for their clinical application. 30–32 , 37 Silica is “generally recognized as safe” by the Food and Drug Administration (FDA) and is currently used as an excipient in some medications. Recently, silica nanoparticles have been approved by the FDA for cancer treatment in several clinical trials for treating cancer.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

Li,

Gao,

et al. 2024

IJN

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Background 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. Methods 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. Results 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 H 2 S 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. Conclusion 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.

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Section: Introductionmentioning

confidence: 99%