Photoresponsive Vaccine‐Like CAR‐M System with High‐Efficiency Central Immune Regulation for Inflammation‐Related Depression. Issue 11 (6th February 2022)

• Record Type: Journal Article
• Authors: Liu, Yu; Hu, Ping; Zheng, Zhiheng; Zhong, Da; Xie, Weichang; Tang, Zhibo; Pan, Bingxing; Luo, Jun; Zhang, Wenhua; Wang, Xiaolei
• Is Part Of: Advanced materials. Volume 34:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-06
• Subjects: inflammation‐related depression -- melatonin -- membrane engineering -- near‐infrared light -- neurological drug delivery; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202108525
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Increasing evidence suggests that activation of microglia‐induced neuroinflammation plays a crucial role in the pathophysiology of depression. Consequently, targeting the central nervous system to reduce neuroinflammation holds great promise for the treatment of depression. However, few drugs can enter the brain via a circulatory route through the blood–brain barrier (BBB) to reach the central nervous system efficiently, which limits the pharmacological treatment for neuropsychiatric diseases. Herein, a light‐responsive system named UZPM, consisting of blue‐emitting NaYF4 :Yb, Tm@zeolitic‐imidazolate framework (UCNP@ZIF‐8), photoacid (PA), and melatonin (MT) is developed to address the above issues. Meanwhile, UZPM is introduced into macrophages by functional liposomes fusion and modified with hydroxylamine groups on the cell surface. Aldehyde‐modified cytotoxic T‐lymphocyte‐associated protein‐4 (CTLA‐4) is used as a chimeric antigen receptor (CAR) targeting group to modify the surface of macrophages by aldehyde/hydroxylamine condensation to precisely target central M1‐type microglia (CAR‐M‐UZPM). Both in vitro and in vivo experiments demonstrate that the CAR‐M‐UZPM drug delivery system can efficiently penetrate the BBB, targeting centrally activated microglia, and thus, inhibiting the M1‐type polarization of microglia, producing continuous vaccine‐like anti‐inflammatory effects that prevent the occurrence and development of inflammation‐related depression. Abstract : The proposed concept of the CAR‐M‐UZPM system makes a breakthrough in the treatment of inflammation‐related depression. By precisely regulating inflammation in the central nervous system, this drug delivery system can exert a light‐response immune regulation effect, inhibit the polarization of M1 type microglia, and produce a vaccine‐like effect to prevent inflammation‐related depression.