Exosome engineering: Current progress in cargo loading and targeted delivery

Todays, nano-pharmaceutics is emerging as an important field of science to develop and improve efficacy of different drugs. Although nutraceuticals are currently being utilized in the prevention and treatment of various chronic diseases such as cancers, a number of them have displayed issues associated with their solubility, bioavailability, and bio-degradability. In the present review, we focus on curcumin, an important and widely used polyphenol, with diverse pharmacological activities such as anti-inflammatory, anti-carcinogenic, anti-viral, etc. Notwithstanding, it also exhibits poor solubility and bioavailability that may compromise its clinical application to a great extent. Therefore, the manipulation and encapsulation of curcumin into a nanocarrier formulation can overcome these major drawbacks and potentially may lead to a far superior therapeutic efficacy. Among different types of nanocarriers, biological and biopolymer carriers have attracted a significant attention due to their pleiotropic features. Thus, in the present review, the potential protective and therapeutic applications of curcumin, as well as different types of bio-nanocarriers, which can be used to deliver curcumin effectively to the different target sites will be discussed.

https://www.mdpi.com/1420-3049/25/3/689/pdf

Curcumin Delivery Mediated by Bio-Based Nanoparticles: A Review.

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood–brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

/pdf/exosomes-derived-from-mesenchymal-stem-cells-repair-a-jz7a2wk1z7.pdf

Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy.

The brain is the body's control center, so when a disease affects it, the outcomes are devastating. Alzheimer's and Parkinson's disease, and multiple sclerosis are brain diseases that cause a large number of human deaths worldwide. Curcumin has demonstrated beneficial effects on brain health through several mechanisms such as antioxidant, amyloid β-binding, anti-inflammatory, tau inhibition, metal chelation, neurogenesis activity, and synaptogenesis promotion. The therapeutic limitation of curcumin is its bioavailability, and to address this problem, new nanoformulations are being developed. The present review aims to summarize the general bioactivity of curcumin in neurological disorders, how functional molecules are extracted, and the different types of nanoformulations available.

Curcumin’s Nanomedicine Formulations for Therapeutic Application in Neurological Diseases

Exosomes are nanoscale-sized membrane vesicles secreted by almost all cell types into the extracellular environment upon fusion of multivesicular bodies and plasma membrane. Biogenesis of exosomes is a protein quality control mechanism, and once released, exosomes transmit signals to other cells. The applications of exosomes have increased immensely in biomedical fields owing to their cell-specific cargos that facilitate intercellular communications with neighboring cells through the transfer of biologically active compounds. The diverse constituents of exosomes reflect their cell of origin and their detection in biological fluids represents a diagnostic marker for various diseases. Exosome research is expanding rapidly due to the potential for clinical application to therapeutics and diagnosis. However, several aspects of exosome biology remain elusive. To discover the use of exosomes in the biomedical applications, we must better understand the basic molecular mechanisms underlying their biogenesis and function. In this comprehensive review, we describe factors involved in exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research, and discuss future perspectives.

/pdf/a-comprehensive-review-on-factors-influences-biogenesis-138h8bhobt.pdf

A Comprehensive Review on Factors Influences Biogenesis, Functions, Therapeutic and Clinical Implications of Exosomes

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.

Curcumin-primed exosomes potently ameliorate cognitive function in AD mice by inhibiting hyperphosphorylation of the Tau protein through the AKT/GSK-3β pathway.

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.

Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles.

Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis

In recent years, numerous studies have confirmed the role of chitosan nanoparticles (CS NPs) as a promising drug delivery carrier for improving the efficiency of anticancer drug in the treatment of cancer. However, the possible biological effects of CS NPs on tumour cells and underlying mechanisms are still unclear. Recently, reactive oxygen species (ROS)-mediated cell apoptosis has been implicated in the regulation of cell death. In this study, we found that CS NPs induced the massive generation of ROS and resulted in apoptosis of hepatocellular carcinoma cells (SMMC-7721) through activating the mitochondrial pathway and endoplasmic reticulum stress. These results suggest an important role of ROS in CS NPs-induced cancer cell death.

Chitosan nanoparticles induced the antitumor effect in hepatocellular carcinoma cells by regulating ROS-mediated mitochondrial damage and endoplasmic reticulum stress

Yibing Jiang

Papers

Curcumin-primed exosomes potently ameliorate cognitive function in AD mice by inhibiting hyperphosphorylation of the Tau protein through the AKT/GSK-3β pathway.

Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles.

Curcumin-laden exosomes target ischemic brain tissue and alleviate cerebral ischemia-reperfusion injury by inhibiting ROS-mediated mitochondrial apoptosis

Chitosan nanoparticles induced the antitumor effect in hepatocellular carcinoma cells by regulating ROS-mediated mitochondrial damage and endoplasmic reticulum stress

Plasma exosomes protect against cerebral ischemia/reperfusion injury via exosomal HSP70 mediated suppression of ROS.