Journal
ADVANCED MATERIALS
Volume 34, Issue 11, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202108525
Keywords
inflammation-related depression; melatonin; membrane engineering; near-infrared light; neurological drug delivery
Categories
Funding
- National Key Research and Development Program of China [2020YFC2005800]
- National Natural Science Foundation of China [31860263, 31970953, 82125010, 81930032, 81760408, 81760505, 32160184]
- Key Youth Project of Jiangxi Province [20202ACB216002, 20192ACB21024, 20212ACB206038]
- Natural Science Foundation of Jiangxi Province [20113BCB22005, 20181BCG42001, G/Y2543, 20192BCB23008, 20181ACG70003]
- Interdisciplinary Innovation Fund of Natural Science, Nanchang University [9167-27060003-ZD2102]
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Microglia-induced neuroinflammation is crucial in the development of depression. Researchers have developed a light-responsive system called UZPM, which can be introduced into macrophages and targeted to centrally activated microglia. Experimental results show that the CAR-M-UZPM drug delivery system can efficiently penetrate the blood-brain barrier, inhibit the M1 polarization of microglia, and prevent the occurrence and development of inflammation-related depression.
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.
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