Ponedal Adam, Zhu Shengshuang, Sprangers Anthony J, Wang Xiao-Qi, Yeo David C, Lio Daniel C S, Zheng Mengjia, Capek Matthew, Narayan Suguna P, Meckes Brian, Paller Amy S, Xu Chenjie, Mirkin Chad A
Department of Chemical and Biological Engineering and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States.
International Institute for Nanotechnology and Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States.
ACS Appl Bio Mater. 2020 Dec 21;3(12):8603-8610. doi: 10.1021/acsabm.0c00990. Epub 2020 Nov 13.
Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.
异常瘢痕形成是伤口愈合过程中调节失调的结果，有效且非侵入性治疗的选择有限。鉴于球形核酸（SNA）能够穿透皮肤并调节其内部的基因表达，我们研究了携带靶向转化生长因子β1（TGF-1）的反义寡核苷酸的金核SNA（AuSNA）和脂质体核SNA（LSNA）是否可作为瘢痕形成的局部治疗方法。重要的是，两种SNA构建体在体外均能明显下调原发性增生性瘢痕和瘢痕疙瘩成纤维细胞中TGF-1蛋白的表达。在体内，通过瘢痕隆起指数测定，局部应用的AuSNA和LSNA下调了TGF-1蛋白表达水平并改善了瘢痕组织学。这些数据强调了SNA作为由基因表达增加驱动的皮肤相关疾病和病症的局部、可自我管理治疗方法的潜力。
