Poly(l ‐Histidine)‐Mediated On‐Demand Therapeutic Delivery of Roughened Ceria Nanocages for Treatment of Chemical Eye Injury
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· 2023
· Open Access
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· DOI: https://doi.org/10.1002/advs.202302174
· OA: W4383873146
Development of topical bioactive formulations capable of overcoming the low bioavailability of conventional eye drops is critically important for efficient management of ocular chemical burns. Herein, a nanomedicine strategy is presented to harness the surface roughness‐controlled ceria nanocages (SRCNs) and poly( l ‐histidine) surface coatings for triggering multiple bioactive roles of intrinsically therapeutic nanocarriers and promoting transport across corneal epithelial barriers as well as achieving on‐demand release of dual drugs [acetylcholine chloride (ACh) and SB431542] at the lesion site. Specifically, the high surface roughness helps improve cellular uptake and therapeutic activity of SRCNs while exerting a negligible impact on good ocular biocompatibility of the nanomaterials. Moreover, the high poly( l ‐histidine) coating amount can endow the SRCNs with an ≈24‐fold enhancement in corneal penetration and an effective smart release of ACh and SB431542 in response to endogenous pH changes caused by tissue injury/inflammation. In a rat model of alkali burn, topical single‐dose nanoformulation can efficaciously reduce corneal wound areas (19‐fold improvement as compared to a marketed eye drops), attenuate ≈93% abnormal blood vessels, and restore corneal transparency to almost normal at 4 days post‐administration, suggesting great promise for designing multifunctional metallic nanotherapeutics for ocular pharmacology and tissue regenerative medicine.
