The status of industrialization and development of exosomes as a drug delivery system: A review

Yin, Yilong; Han, Xing; Li, Cheng; Sun, Tonghui; Li, Kailin; Liu, Xionghao; Liu, Mujun

doi:10.3389/fphar.2022.961127

Cited by 8 publications

(7 citation statements)

References 66 publications

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“…Another challenge that needs to be addressed is the low drug loading efficiencies reported when loading Exos [ 65 , 66 ]. Conventional strategies such as lentiviral transfection and co-incubation methods have low loading capacities, while other exogenous methods with higher loading capabilities such as ultrasound and electroporation can damage vesicles or cause Exo aggregation [ 67 , 68 ]. These issues need to be addressed while exploring the therapeutic potential of this delivery platform using TTC-targeted Exos loaded with therapeutic bioactive drugs or substances in the PNS.…”

Section: Discussionmentioning

confidence: 99%

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Krishnan,

Alimi,

Pan

et al. 2024

Pharmaceutics

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The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived exosomes (Exos) have gained widespread attention as biocompatible vehicles for therapeutics in clinical applications. However, engineering targeted Exos for the peripheral nervous system (PNS) is still challenging. This study aims to develop a targeted Exo delivery system specifically designed for presynaptic terminals of peripheral nerve tissue. The clostridium neurotoxin, tetanus toxin-C fragment (TTC), was tethered to the surface of red blood cell (RBC)-derived Exos via a facile and efficient bio-orthogonal click chemistry method without a catalyst. Additionally, Cyanine5 (Cy5), a reactive fluorescent tag, was also conjugated to track Exo movement in both in vitro and in vivo models. Subsequently, Neuro-2a, a mouse neuronal cell line, was treated with dye-labeled Exos with/without TTC in vitro, and the results indicated that TTC-Exos exhibited more efficient accumulation along the soma and axonal circumference, compared to their unmodified counterparts. Further investigation, using a mouse model, revealed that within 72 h of intramuscular administration, engineered TTC-Exos were successfully transported into the neuromuscular junction and sciatic nerve tissues. These results indicated that TTC played a crucial role in the Exo delivery system, improving the affinity to peripheral nerves. These promising results underscore the potential of using targeted Exo carriers to deliver therapeutics for treating peripheral neuropathies.

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Section: Discussionmentioning

confidence: 99%

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Krishnan,

Alimi,

Pan

et al. 2024

Pharmaceutics

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“…The mononuclear phagocytic system (MPS) plays a major role in clearing exosomes from circulation. Although exosomes possess a slightly negative surface charge which may reduce MPS-mediated clearance compared to positively charged nanoparticles (NPs) [ 138 ], their circulation time could be adversely affected by phosphatidylserine (PS), a negatively charged lipid present on their surface [ 139 ]. Appropriate surface modifications could improve the rapid clearance of exosomes from somatic circulation.…”

Section: In Vivo Characteristicsmentioning

confidence: 99%

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

Yang,

Li,

et al. 2024

J Nanobiotechnol

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Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy. Graphical Abstract

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“…These vesicles are believed to play an intricate role in cell-to-cell communications [ 113 , 114 , 115 ]. The idea of using lipid bilayer membrane vesicles for the delivery of bioactive molecules to cells has been readily adopted by the drug delivery field of research [ 116 , 117 ]. The following two different methodologies are currently utilized: that of liposomes, and that of exosomes [ 118 , 119 ].…”

Section: Principles Of Phage Displaymentioning

confidence: 99%

Improving Pharmacokinetics of Peptides Using Phage Display

Asar,

Newton-Northup,

Soendergaard

2024

Viruses

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Phage display is a versatile method often used in the discovery of peptides that targets disease-related biomarkers. A major advantage of this technology is the ease and cost efficiency of affinity selection, also known as biopanning, to identify novel peptides. While it is relatively straightforward to identify peptides with optimal binding affinity, the pharmacokinetics of the selected peptides often prove to be suboptimal. Therefore, careful consideration of the experimental conditions, including the choice of using in vitro, in situ, or in vivo affinity selections, is essential in generating peptides with high affinity and specificity that also demonstrate desirable pharmacokinetics. Specifically, in vivo biopanning, or the combination of in vitro, in situ, and in vivo affinity selections, has been proven to influence the biodistribution and clearance of peptides and peptide-conjugated nanoparticles. Additionally, the marked difference in properties between peptides and nanoparticles must be considered. While peptide biodistribution depends primarily on physiochemical properties and can be modified by amino acid modifications, the size and shape of nanoparticles also affect both absorption and distribution. Thus, optimization of the desired pharmacokinetic properties should be an important consideration in biopanning strategies to enable the selection of peptides and peptide-conjugated nanoparticles that effectively target biomarkers in vivo.

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The status of industrialization and development of exosomes as a drug delivery system: A review

Cited by 8 publications

References 66 publications

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

Improving Pharmacokinetics of Peptides Using Phage Display

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