Alzheimer's disease (AD) is the progressive development of fatal neurodegenerative diseases. Owing to the unclearness of the pathogenesis of AD and the failure of the drug to cross the blood–brain barrier (BBB), there is currently a lack of effective diagnostic and therapeutic approaches in the treatment of AD. The aim of this study was to design exosomes (Exo) as a specifically designed carrier able to carry curcumin (cur) to prevent neuronal death in vitro and in vivo to alleviate the AD symptoms. Our results demonstrated that Exo improved the solubility and bioavailability of cur and increased drug penetration across the BBB by specific active targeting between Exo, inheriting the lymphocyte function-associated antigen 1 (LFA-1) and endothelial intercellular adhesion molecule 1 (ICAM-1). Exosomes derived from curcumin-treated (primed) cells (Exo-cur) can better prevent the death of neurons in vitro and in vivo to relieve the symptoms of AD by inhibiting phosphorylation of the Tau protein through activating the AKT/GSK-3β pathway. Our results suggested that Exo-cur featured highly effective BBB-crossing via receptor-mediated transcytosis to access brain tissues and inhibited Tau phosphorylation, holding great potential in improving targeted drug delivery and the recovery of neuronal function in AD therapy.

It is reported that quercetin (Que) can prevent tau pathology and induce neuroprotection by improving cognitive and functional symptoms in the treatment of Alzheimer’s disease (AD). However, its clinical application has been limited due to its poor brain targeting and bioavailability. Exosomes are considered as cargo carriers for intercellular communication and especially serve as a natural and important drug brain delivery platform for achieving better treatment of central neurological diseases. Here, we developed plasma exosomes (Exo) loaded with Que (Exo-Que) to improve the drug bioavailability, enhance the brain targeting of Que and potently ameliorate cognitive dysfunction in okadaic acid (OA)-induced AD mice. Our results showed that Exo-Que improved brain targeting of Que as well as significantly enhanced bioavailability of Que. Furthermore, compared with free Que, Exo-Que better relieved the symptoms of AD by inhibiting cyclin-dependent kinase 5 (CDK5)-mediated phosphorylation of Tau and reducing formation of insoluble neurofibrillary tangles (NFTs), suggesting its therapeutic potential for better treatment of AD.

Chronic, subclinical inflammation was often observed in the diabetic wound area, causing inadequate and delayed wound-healing effects by failing to initiate cell migration, proliferation, and extracellular matrix deposition. Therefore, we presented macrophage-derived exosomes (Exos) and explored their potential for inhibiting inflammation and accelerating diabetic wound healing in a skin defect, diabetic rat model. A thorough investigation demonstrated that Exos exerted anti-inflammatory effects by inhibiting the secretion of pro-inflammatory enzymes and cytokines. Furthermore, they accelerated the wound-healing process by inducing endothelial cell proliferation and migration to improve angiogenesis and re-epithelialization in diabetic wounds.

Inflammation occurs throughout the progression of cerebral ischemia/reperfusion and mediates myriads of pathological events following an ischemic insult. After ischemic stroke, inflammation was significantly triggered and microglia were activated to phenotypes (M1) typically releasing pro-inflammatory mediators, thus inducing neuron apoptosis and exacerbating brain injury. Therefore, shifting the polarization of microglia from the detrimental pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems a promising therapeutic strategy in ischemic stroke. In this study we aimed to investigate the effects of exosomes (Ex) secreted from the lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cell line (LPS-Ex) on inducing neuroprotection and functional improvement after ischemic stroke by enhancing microglial M2 polarization. The results showed that LPS-Ex treatment exhibited more potent anti-inflammatory and neuroprotective effects in vitro; furthermore it significantly reduced the brain infarct volume and improved neurological function in a rat model of transient focal cerebral ischemia. The beneficial effects of LPS-Ex in ischemic stroke were associated with enhancing microglial polarization from the M1 phenotype to the M2 phenotype and inhibiting inflammation response. In conclusion, LPS-Ex protected against cerebral ischemia by skewing the microglial functional polarity from M1 toward an anti-inflammatory M2 phenotype. It may serve as a novel therapeutic strategy for neuroprotection and functional recovery upon ischemic stroke onset.

A targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity. We reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44. Our new findings suggested that HA-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS). Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells. Biocompatible and biodegradable HA-coated chitosan NPs were developed to encapsulate a chemotherapeutic drug (5-Fu) to enhance drug accumulation in tumor cells and to improve the agent’s antitumor efficiency by offering targeted drug delivery via CD44.