Harnessing the Therapeutic Potential of Extracellular Vesicles for Biomedical Applications Using Multifunctional Magnetic Nanomaterials

Abstract

muscle cells, and stem cells. [5][6][7][8][9][10][11][12] Although initially considered as membrane debris with no biological significance, the crucial roles of EVs in immune surveillance, viral infection, blood coagulation, tissue repair, and stem cell maintenance, have been sequentially identified since 1996. [6,[13][14][15][16][17][18][19] Additionally, biomolecular compositions inside EVs have also been closely associated with the pathology of various kinds of diseases such as cancers, musculoskeletal diseases, as well as degenerative neurological disorders. [20][21][22] As a result of the fundamental role of EVs in mediating cell-to-cell communications and regulating various tissue functions, there has been a critical need to develop novel therapeutics and diagnostics (or theranostics) using EVs and their associated biomolecules. [23] For example, cellfree therapy using EVs derived from mesenchymal stem cells (MSCs) has been exploited and is currently under clinical trials to enhance tissue regeneration after cardiac infarction. [6,7,17,18] Similarly, EVs capable of crossing the bloodbrain barrier (BBB) have been utilized for intranasal delivery of therapeutics for treating central nervous system (CNS) injuries. [24][25][26][27] Moreover, minimally invasive, highly sensitive/accurate diagnosis of cancer metastasis, viral infection, Prion diseases, Alzheimer's disease (AD), and Parkinson's disease (PD), has also been realized by analyzing the biomolecular formulation of EVs extracted from human body fluids. [28,29] Although the potential of using EVs for theranostic applications is enormous, their current clinical translation is still impeded by several critical barriers, which can be attributed mainly to the high heterogeneity of EVs. In general, there are four levels of heterogeneity of EVs, including size, composition, function, and source heterogeneities. [2,30] Specifically, most clinical applications often require a well-defined source of therapeutics. Sizes, compositions, functions, and sources have all been closely associated with the outcome of clinical treatment and diagnostic diseases. [30][31][32][33][34][35][36] Having the ability to isolate a specific population of EVs with well-defined sizes, biomolecular contents, disease-specific biological functions, and biodistributions would be crucial for the clinical application of EVs. Failing to achieve this can lead to compromised therapeutic effects and sometimes even adverse outcomes. For example, the multifaceted roles of EVs have been identified for regulating Extracellular vesicles (e.g., exosomes) carrying various biomolecules (e.g., proteins, lipids, and nucleic acids) have rapidly emerged as promising platforms for many biomedical applications. Despite their enormous potential, their heterogeneity in surfaces and sizes, the high complexity of cargo biomolecules, and the inefficient uptake by recipient cells remain critical barriers for their theranostic applications. To address these critical issues, multifunctional nanomaterials, such as magn...

Immunomagnetic Separation Method Integrated with the Strep-Tag II System for Rapid Enrichment and Mild Release of Exosomes

“…Magnetic nanoparticles have a great potential in biomedical applications because of their homogeneous reaction process, fast external magnetic response, and large surface area. 48 Importantly, many of target biomolecules (proteins, lipids, etc.) are found on the phospholipid membrane of exosomes, which provides an excellent opportunity for highly selective isolation of exosomes.…”

Current Status, Opportunities, and Challenges of Exosomes in Oral Cancer Diagnosis and Treatment

“… 156 A related review has also described multifunctional nanomaterials with tunable physical, chemical and biological properties that may play a key role in exosome-based drug delivery. 157 This combination of nanoparticles and exosomes allows for therapeutic implementation on the same platform and has the advantages of providing targeting, improving dispersion, and avoiding clearance by the immune system. This approach of targeted transport of therapeutic exosomes by the combined action of magnetic nanoparticles and external magnetic fields may not only improve the precise localization of the drug in the organism, but also improve drug retention, prolong drug half-life, reduce drug dose, and improve efficacy (even in high blood flow systems).…”

Multifunctional Magnetic Nanoparticles for Dynamic Imaging and Therapy

“…The MNPs are widely utilized and studied for therapeutic applications to treat malignant cells using their unique characteristics. [41,42] Representatively, the hyperthermal effect of MNPs has been employed for tumor treatment. To elaborate, MNPs generate high heat when subjected to either pulsed or alternating high frequency of electromagnetic fields [43] owing to induced eddy currents, magnetic hysteresis loss, Néel relaxation, and Brownian relaxation.…”