Emerging prospects of extracellular vesicles for brain disease theranostics

Wang, Ruoning; Wang, Xiaohong; Zhang, Yuting; Zhao, Huacong; Cui, Jiwei; Li, Junsong; Di, Liuqing

doi:10.1016/j.jconrel.2021.12.024

Cited by 34 publications

(19 citation statements)

References 252 publications

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“…The release behavior of CpG-EXO/TGM in physiological (pH 7.4) and GBM cells (pH 5.4) was studied. CpG-EXO/TGM were dialyzed (12−14 kDa) against PBS at pH 7.4 or pH 5.4 with constant shaking at 37 °C at 150 rpm. Two mL samples were taken at 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h, and an equal volume of corresponding release medium was supplemented.…”

Section: Methodsmentioning

confidence: 99%

“…Although the preparation process of many drug-loaded lipid NPs has been very mature, there are still many problems waiting for us to solve. Long circulation and efficient brain targeting are essential for nanodrug delivery systems to treat GBM . Recently, biomimetic drug delivery systems based on cell membranes and extracellular vesicles have been widely used to overcome barriers to brain drug delivery. − It has been demonstrated that the delivery of CpG ODNs through erythrocyte membrane biomimetic NPs can achieve significant anti-GBM efficacy .…”

mentioning

confidence: 99%

“…Since EXO are endogenous substances, they have lower immunogenicity than other commonly used nanocarriers. They can escape the phagocytosis of the mononuclear macrophage system, thereby achieving long circulation in the body . Targeted delivery mediated by ligand receptors is currently the primary strategy for designing targeted nanodrug delivery systems.…”

mentioning

confidence: 99%

“…They can escape the phagocytosis of the mononuclear macrophage system, thereby achieving long circulation in the body. 37 Targeted delivery mediated by ligand receptors is currently the primary strategy for designing targeted nanodrug delivery systems. The BBB/BBTB and GBM cells express abundant transferrin (Tf) receptor (TfR).…”

mentioning

confidence: 99%

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Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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Effective drug delivery and prevention of postoperative recurrence are significant challenges for current glioblastoma (GBM) treatment. Poor drug delivery is mainly due to the presence of the blood–brain barrier (BBB), and postoperative recurrence is primarily due to the resistance of GBM cells to chemotherapeutic drugs and the presence of an immunosuppressive microenvironment. Herein, a biomimetic nanodrug delivery platform based on endogenous exosomes that could efficiently target the brain without targeting modifications and co-deliver pure drug nanomicelles and immune adjuvants for safe and efficient chemo-immunotherapy against GBM is prepared. Inspired by the self-assembly technology of small molecules, tanshinone IIA (TanIIA) and glycyrrhizic acid (GL), which are the inhibitors of signal transducers and activators of transcription 3 from traditional Chinese medicine (TCM), self-assembled to form TanIIA-GL nanomicelles (TGM). Endogenous serum exosomes are selected to coat the pure drug nanomicelles, and the CpG oligonucleotides, agonists of Toll-like receptor 9, are anchored on the exosome membrane to obtain immune exosomes loaded with TCM self-assembled nanomicelles (CpG-EXO/TGM). Our results demonstrate that CpG-EXO/TGM can bind free transferrin in blood, prolong blood circulation, and maintain intact structures when traversing the BBB and targeting GBM cells. In the GBM microenvironment, the strong anti-GBM effect of CpG-EXO/TGM is mainly attributed to two factors: (i) highly efficient uptake by GBM cells and sufficient intracellular release of drugs to induce apoptosis and (ii) stimulation of dendritic cell maturation and induction of tumor-associated macrophages polarization by CpG oligonucleotides to generate anti-GBM immune responses. Further research found that CpG-EXO/TGM can not only produce better efficacy in combination with temozolomide but also prevent a postoperative recurrence.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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“…As the BBB is one of the major obstacles in treating NDs, it is important to understand how EVs interact with the BBB. EVs secreted by brain cells can cross the BBB into the bloodstream, and circulating EVs can cross the BBB into the brain [90] . To date, exosomes and receiving cells interact in five ways: recognition by a protein G-coupled receptor on the cell surface, adhesion and fusion to the cell surface, micropinocytosis, non-specific or lipid rafts, and receptor-mediated transcytosis [91] .…”

Section: Evs For Drug Deliverymentioning

confidence: 99%

Extracellular Vesicle-based Drug Delivery System Boosts Phytochemicals’ Therapeutic Effect for Neurodegenerative Diseases

Liao

Qiao

2022

Acupuncture and Herbal Medicine

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Neurodegenerative diseases (NDs) are a major threat to the elderly, and efficient therapy is rarely available. A group of phytochemicals has been shown to ameliorate NDs; however, poor stability, low bioavailability, and reduced drug accumulation in brain tissue limit their application in NDs. Therefore, a targeted drug delivery system is a feasible treatment strategy for NDs. Extracellular vesicles (EVs) possess many favorable bioactivities and are excellent carriers for targeting brain tissue. This review summarizes EVs as novel phytochemical carriers in ND therapy. First, we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs. Second, we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs. Finally, encapsulation strategies for phytochemicals in EVs are particularly reviewed, as they are critical for obtaining high loading efficacy and stable drug delivery systems. This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment. Therefore, the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.

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Nano‐Engineering Strategies for Tumor‐Specific Therapy

Li,

Xie,

Nie.

2024

ChemMedChem

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Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, and limited tumor accumulation. Hence, engineering modification of NDSs aiming at promoting tumor‐specific therapy and avoiding systemic toxicity is usually needed. An NDS integrating various functionalities, including flexible camouflage, specific biorecognition, and sensitive stimuli‐responsiveness, into one sequence would be "smart" and highly effective. Herein, we systematically summarize the related principles, methods, and progress. At the end of the review, we predict the obstacles to precise nanoengineering and prospects for the future application of NDSs.

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Emerging prospects of extracellular vesicles for brain disease theranostics

Cited by 34 publications

References 252 publications

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Extracellular Vesicle-based Drug Delivery System Boosts Phytochemicals’ Therapeutic Effect for Neurodegenerative Diseases

Nano‐Engineering Strategies for Tumor‐Specific Therapy

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