pH-responsive ZIF-8-based nitazoxanide nanodelivery system for synergistic inhibition of retinoblastoma growth.
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Retinoblastoma (RB) remains a predominant intraocular malignancy in the pediatric population, and its clinical management is significantly impeded by limited blood-retinal barrier (BRB) penetration, the development of multidrug resistance, and severe systemic toxicity. This study aims to develop a novel nanodelivery system based on Zeolitic Imidazolate Framework-8 (ZIF-8) to overcome the limited bioavailability of the antiparasitic drug nitazoxanide (NTZ), and to enhance its anti-retinoblastoma efficacy. We successfully engineered ZIF-8@NTZ nanoparticles characterized by a robust core-shell architecture. Characterization results showed that the particles exhibited high drug loading capacity (approximately 58.628%), suitable particle size (∼231 nm), and significant pH-responsive drug release properties. In vitro assays indicated that ZIF-8@NTZ exerted potent inhibition on RB cell proliferation and induced apoptosis. In vivo experiments further confirmed that ZIF-8@NTZ could significantly inhibit tumor growth. This study indicates that the ZIF-8@NTZ nanosystem provides a promising strategy for the targeted therapy of retinoblastoma.