Ju Minzi, Zhang Zhongkun, Gao Feng, Chen Gang, Zhao Sibo, Wang Dan, Wang Huijuan, Jia Yanpeng, Shen Ling, Yuan Yonggui, Yao Honghong
Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Adv Healthc Mater. 2024 Dec;13(30):e2402219. doi: 10.1002/adhm.202402219. Epub 2024 Sep 10.
Major depressive disorder (MDD) is a prevalent mental disorder that significantly impacts social and psychological function, but no effective medication is currently available. Circular RNAs (circRNAs) have been reported to participate in the pathogenesis of MDD which are envisioned as promising therapeutic targets. However, nonviral-based delivery strategies targeting circRNA against MDD are not thoroughly investigated. Here, it is identified that circATF7IP is significantly upregulated in plasma samples and positively correlated with 24-Hamilton Depression Scale (HAMD-24) scores of MDD patients. Synergistic amine lipid nanoparticles (SALNPs) are designed to deliver siRNA targeting circATF7IP (si-circATF7IP) into the hippocampus brain region by intranasal administration. Intranasal delivery of SALNP-si-circATF7IP successfully alleviated the depressive-like behaviors in the LPS-induced mouse depression model via decreasing CD11bCD45 microglia population and pro-inflammatory cytokine productions (TNF-α and IL-6). These results indicate that the level of circATF7IP positively correlates with MDD pathogenesis, and SALNP delivery of si-circATF7IP via intranasal administration is an effective strategy to ameliorate LPS-induced depressive-like behaviors.
重度抑郁症（MDD）是一种普遍存在的精神障碍，会对社会和心理功能产生重大影响，但目前尚无有效的药物治疗。据报道，环状RNA（circRNA）参与了MDD的发病机制，有望成为有前景的治疗靶点。然而，针对circRNA治疗MDD的非病毒递送策略尚未得到充分研究。在此研究中，发现circATF7IP在MDD患者的血浆样本中显著上调，且与24项汉密尔顿抑郁量表（HAMD-24）评分呈正相关。设计了协同胺脂质纳米颗粒（SALNP），通过鼻腔给药将靶向circATF7IP的小干扰RNA（si-circATF7IP）递送至海马脑区。鼻腔递送SALNP-si-circATF7IP通过减少CD11bCD45小胶质细胞数量和促炎细胞因子（TNF-α和IL-6）的产生，成功缓解了脂多糖诱导的小鼠抑郁模型中的抑郁样行为。这些结果表明，circATF7IP水平与MDD发病机制呈正相关，通过鼻腔给药SALNP递送si-circATF7IP是改善脂多糖诱导的抑郁样行为的有效策略。
