Two-dimensional ultrathin Ti(3)C(2) MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification

二维超薄Ti(3)C(2) MXene纳米片包覆人工晶状体,用于协同光热疗法和近红外可控雷帕霉素释放疗法治疗后囊膜混浊

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Abstract

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti(3)C(2)-IOL), prepared from two-dimensional ultrathin Ti(3)C(2) MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti(3)C(2) was prepared via electrostatic self-assembly of Ti(3)C(2) and Rapa, with a loading capacity of Rapa at 92%. Ti(3)C(2) was used as a drug delivery reservoir of Rapa. Rapa@Ti(3)C(2)-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti(3)C(2)-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti(3)C(2) coating effectively eliminated the LECs around Rapa@Ti(3)C(2)-IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm(-2)). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti(3)C(2)-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti(3)C(2)-IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti(3)C(2) MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

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