Nerve growth factor loaded macrophage-derived nanovesicles for inhibiting neuronal apoptosis after spinal cord injury

Abstract

Spinal cord injury (SCI) is an extremely destructive central nervous system lesion. Studies have shown that NGF can promote nerve regeneration after SCI. However, it cannot produce the desired effect due to its stability in the body and is difficulty in passing through the blood-brain barrier. In this study, we prepared nanovesicles derived from macrophage membrane encapsulating NGF (NGF-NVs) as a drug carrier for the treatment of SCI. Cell experiments showed that NGF-NVs were effectively taken up by PC12 cells and inhibited neuronal apoptosis. In vivo imaging experiments, a large quantity of NGF was delivered to the injured site with the aid of the good targeting of NVs. In animal experiments, NGF-NVs improved the survival of neurons by significantly activating the PI3K/AKT signaling pathway and had good behavioral and histological recovery effects after SCI. Therefore, NVs are a potential drug delivery vector for SCI therapy.

The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities

“…Nerve growth factor (NGF) is an important member of the neurotrophic factor family with important roles in neuron development, axon growth, neurotransmitter synthesis and apoptosis 220 . Xia et al 221 showed that NGF inhibited oxidative stress‐induced apoptosis in an in vitro model of SCI. NGF significantly activated the PI3K/AKT signalling pathway, promoted the expression of the anti‐apoptotic protein Bcl‐2 and inhibited the expression of the proapoptotic proteins Bax and caspase‐3.…”

Macrophage cell membrane-based nanoparticles: a new promising biomimetic platform for targeted delivery and treatment

“…F Co-localization of membranes (red) and core (green) by CLSM. Adapted with permission from [ 131 ], copyright © 2022 Elsevier B.V. G Representative SDS-PAGE result showing the membrane proteins analysis of PLGA cores (lane 1), AM membranes (lane 2), AM vesicles (lane 3), TN@AM NPs (lane 4), and AM cell lysate (lane 5). Lane M: marker.…”

“…Good targeting capacity 3. Good behavioral and histological recovery effects [ 131 ] Acute ischemic stroke Primary macrophage MnO 2 Fingolimod In vitro: SH-SY5Y cells In vivo: rat model of transient middle cerebral artery occlusion/reperfusion 1. Actively accumulation in the damaged brain 2.…”

“…Macrophages are characterized by chemotaxis to inflammatory sites, penetrating blood vessels, and targeting the damaged central nervous system through the interaction of adhesion factors and integrins [ 130 ]. Xia’s group encapsulated nerve growth factor (NGF) into the macrophage membrane (NGF-NVs) to treat SCI [ 131 ]. Cell viability assays showed that NGF-NVs were effectively taken up by PC12 cells and inhibited neuronal apoptosis.…”

Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury

“…In addition to the above cell membranes, macrophage membranes are commonly used owing to the advantages of low immunogenicity, good biocompatibility, good biodegradability, long circulation, tendency to inflammation, and easy crossing of the blood–brain barrier. Our previous research demonstrated that macrophage-derived nanovesicles encapsulated with nerve growth factor (NGF) can play a neuroprotective role and promote the recovery of motor function after SCI [19] . Therefore, macrophage membranes-derived drug delivery carriers have high potential anti-inflammatory, neuroprotective and motor recovery applications after SCI.…”