Yu Fei, Zhao Xuan, Wang Qian, Fang Po-Han, Liu Liu, Du Xinyue, Li Weihua, He Dalian, Zhang Tingting, Bai Ying, Liu Lu, Li Saiqun, Yuan Jin
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510623, China.
Guangdong Engineering Technology Research Centre for Functional Biomaterials, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510006, China.
ACS Nano. 2024 Jul 24. doi: 10.1021/acsnano.4c00423.
Corneal alkali burns represent a prevalent ophthalmic emergency with the potential to induce blindness. The main contributing mechanisms include excessive inflammation and delayed wound healing. Existing clinical therapies have limitations, promoting the exploration of alternative methods that offer improved efficacy and reduced side effects. Adipose-derived stem cell-exosome (ADSC-Exo) has the potential to sustain immune homeostasis and facilitate tissue regeneration. Nevertheless, natural ADSC-Exo lacks disease specificity and exhibits limited bioavailability on the ocular surface. In this study, we conjugated antitumor necrosis factor-α antibodies (aT) to the surface of ADSC-Exo using matrix metalloproteinase-cleavable peptide chains to create engineered aT-Exo with synergistic effects. In both in vivo and in vitro assessments, aT-Exo demonstrated superior efficacy in mitigating corneal injuries compared to aT alone, unmodified exosomes, or aT simply mixed with exosomes. The cleavable conjugation of aT-Exo notably enhanced wound healing and alleviated inflammation more effectively. Simultaneously, we developed poly(vinyl alcohol) microneedles (MNs) for precise and sustained exosome delivery. The in vivo results showcased the superior therapeutic efficiency of MNs compared with conventional topical administration and subconjunctival injection. Therefore, the bioactive nanodrugs-loaded MNs treatment presents a promising strategy for addressing ocular surface diseases.
角膜碱烧伤是一种常见的眼科急症，有致盲风险。主要致病机制包括过度炎症反应和伤口愈合延迟。现有的临床治疗方法存在局限性，促使人们探索疗效更佳、副作用更小的替代方法。脂肪来源干细胞外泌体（ADSC-Exo）具有维持免疫稳态和促进组织再生的潜力。然而，天然的ADSC-Exo缺乏疾病特异性，且在眼表的生物利用度有限。在本研究中，我们利用基质金属蛋白酶可裂解肽链将抗肿瘤坏死因子-α抗体（aT）偶联到ADSC-Exo表面，制备出具有协同效应的工程化aT-Exo。在体内和体外评估中，与单独使用aT、未修饰的外泌体或简单混合的aT与外泌体相比，aT-Exo在减轻角膜损伤方面显示出更优的疗效。aT-Exo的可裂解偶联显著增强了伤口愈合，并更有效地减轻了炎症。同时，我们开发了聚（乙烯醇）微针（MNs）用于精确且持续的外泌体递送。体内实验结果表明，与传统的局部给药和结膜下注射相比，MNs具有更高的治疗效率。因此，负载生物活性纳米药物的MNs治疗为解决眼表疾病提供了一种有前景的策略。
