Photoresponsive Vaccine‐Like CAR‐M System with High‐Efficiency Central Immune Regulation for Inflammation‐Related Depression

Abstract

Traditional antidepressants are mainly based on the "monoamine hypothesis," aiming to increase dopamine, serotonin, and norepinephrine levels in the brain. [2] However, the slow onset time (≈four weeks) and limited efficacy (≈30% of patients do not respond to at least two antidepressants) cannot meet the growing clinical demand for the treatment of depression. [3] Therefore, it is of great importance and urgency to develop new antidepressants strategies. Accumulating evidence has indicated that inflammation plays an essential role in the pathogenesis of depression. [4] For example, previous studies have shown that patients with various inflammation-related diseases such as postpartum, [5] diabetes, [6] stroke, [7] coronavirus disease-19 (COVID-19) [8] , and cancer treated with interferon-alpha [9] are more likely to develop depression disorder. Peripheral inflammation elicits the secretion of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which can pass the blood-brain barrier (BBB) into the central nervous system, and activate and polarize microglial cells toward the pro-inflammatory M1 phenotype. [10] Then, the M1 polarized microglia cells further produce pro-inflammatory cytokines, which lead to neuronal dysfunction and the progress 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 NaYF 4 :Yb,

ROS-Targeted Depression Therapy via BSA-Incubated Ceria Nanoclusters

“…The therapeutic effects of CeO 2 @BSA nanoclusters were determined using the chronic restraint stress (CRS)-induced depressive model, a more credible depression model to simulate human stress in life, compared with other inflammatory models such as the lipopolysaccharide (LPS)-induced one . Our study proved the validity by directly using nanodrugs as antidepression drugs, acting as a nanocarrier by loading antidepressants, , which, in turns, greatly expands the application of nanomaterials in depression treatment.…”

TJ-M2010-5, a novel CNS drug candidate, attenuates acute cerebral ischemia-reperfusion injury through the MyD88/NF-κB and ERK pathway

“…The BBB is an interface that controls the exchange of substances between the CNS and blood, which makes it difficult to develop drugs ( Banks, 2016 ). Currently, many drugs are unable to enter the CNS efficiently through the BBB, which limits the development of therapies for CNS diseases ( Chiu et al, 2021 ; Liu et al, 2021 ). Microglia are resident macrophages in the brain.…”

A self-developed MyD88 inhibitor across the blood-brain barrier fully reverses acute cerebral ischemia-reperfusion injury

“…BBB is the interface that controls the exchange of substances between the central nervous system (CNS) and blood, which brings di culty in developing drugs that can cross such barrier [36]. Currently, not many drugs can enter the CNS e ciently through the BBB, which limits the development of therapies for brain diseases [37,38]. Microglia are resident macrophages in the brain.…”