TRPV1-targeted ion-responsive hydrogel against pyroptosis of dry eye disease

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Vol. 499; p. 156155
• Main Authors: Ding, Xiangyu, Mu, Jingqing, Mi, Baoyue, Yuan, Zhengxi, Fang, Xiaolong, Ji, Xiaoyuan, Yuan, Xiaoyong, Guo, Shutao, Hua, Xia
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2024
• Subjects: Calcium signaling; Dry eye disease; In situ gelling system; Pyroptosis; Transient receptor potential vanilloid 1; Calcium signaling; Transient receptor potential vanilloid 1; Pyroptosis; In situ gelling system; Dry eye disease
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.156155

[Display omitted] •Tear triggers in situ gelation of co-assembled nanofibers KFQ12/V1-Cal.•Hydrogel facilitates corneal wound healing and sustained drug release.•V1-Cal, an inhibitor of TRPV1 channel, is a potential agent for dry eye treatment.•TRPV1-Ca2+-Pyroptosis axis serves as a potential mechanism for dry eye disease. Dry eye disease (DED) is a complex ocular surface abnormality characterized by tear film hyperosmolarity, inflammation, and damage. Left untreated, DED can lead to a self-perpetuating vicious cycle of worsening symptoms. Existing treatments for DED face challenges related to limited drug delivery to the ocular surface and potential side effects from nonspecific drug targeting. In an effort to address these issues, we developed a novel ion-responsive in situ gelling system targeting the transient receptor potential vanilloid 1 (TRPV1), based on co-assembly of the hydrogelator KFQ12 with the functional peptide V1-Cal. The KFQ12/V1-Cal (KVC) aqueous solution, when dripped and mixed with the ionic tear film on the ocular surface, rapidly transformed into a honeycomb-like hydrogel. This hydrogel exhibited prolonged retention on the ocular surface, serving as a stable scaffold for corneal epithelium regeneration and providing protection against external pathogens while maintaining gas exchange. In a murine model of DED, the KVC hydrogel demonstrated superior therapeutic efficacy due to its sustained release characteristics and specific inhibition of the TRPV1 channel activated by hyperosmotic or desiccating stress. By performing transcriptome sequencing and experimental validation both in vivo and in vitro, we confirmed the mechanism of the TRPV1-Ca2+-Pyroptosis axis in the pathogenesis of DED. Our research provides novel perspectives on the understanding and treatment of DED, and introduces a potential ocular surface drug delivery system characterized by superior biosafety, prolonged retention, and improved therapeutic outcomes.