Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development

Jan, Arif Tasleem; Rahman, Safikur; Badierah, Raied; Lee, Eun Ju; Mattar, Ehab H.; Redwan, Elrashdy M.; Choi, Inho

doi:10.3390/cancers13051157

Cited by 28 publications

(21 citation statements)

References 247 publications

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“…Many exosomes have these characteristics. In addition, they are small, have extremely low toxicity, and can cause a low rate of long-term accumulation in organs and tissues [66,127,167]. They can also cross various biological fluids and pass through plasma membranes, thus delivering therapeutic compounds into the cytoplasm of target cells [147].…”

Section: Drug Delivery Of Therapeutic Biomaterials Through Different Administration Routesmentioning

confidence: 99%

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

Kučuk

Primožič

Knez

et al. 2021

IJMS

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Exosomes are becoming increasingly important therapeutic biomaterials for use in a variety of therapeutic applications due to their unique characteristics, especially due to the ineffectiveness and cytotoxicity of some existing therapies and synthetic therapeutic nanocarriers. They are highly promising as carriers of drugs, genes, and other therapeutic agents that can be incorporated into their interior or onto their surface through various modification techniques to improve their targeting abilities. In addition, they are biocompatible, safe, and stable. The review focuses on different types of exosomes and methods of their preparation, including the incorporation of different kinds of cargo, especially for drug delivery purposes. In particular, their importance and effectiveness as delivery vehicles of various therapeutic agents for a variety of therapeutic applications, including different diseases and disorders such as cancer treatment, cardiovascular and neurodegenerative diseases, are emphasized. Administration routes of exosomes into the body are also included. A novelty in the article is the emphasis on global companies that are already successfully developing and testing such therapeutic biomaterials, with a focus on the most influential ones. Moreover, a comparison of the advantages and disadvantages of the various methods of exosome production is summarized for the first time.

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Section: Drug Delivery Of Therapeutic Biomaterials Through Different Administration Routesmentioning

confidence: 99%

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

Kučuk

Primožič

Knez

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…ATPase, adenosine triphosphatase; CD, cluster of differentiation; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HSP, heat shock protein; ICAM-1, intercellular adhesion molecule-1; LAM 1/2, lysosomal-associated membrane protein 1/2; MHC, major histocompatibility complex; miRNA, microRNA; mRNA, messenger RNA; MVB, multivesicular body; PGRL, PG regulatory-like protein; pgk1, phosphoglycerate kinase 1. [Adopted from Jan et al (2021) distributed under the Creative Commons Attribution Licens].…”

Section: Biogenesis Of Exosomesmentioning

confidence: 99%

“…The exosomal indigenous cargo is mostly rich in proteins, lipids, sugars, and nucleic acids [messenger RNAs (mRNAs), microRNAs (miRNAs), and mitochondrial DNA (mtDNA), etc.] (Jan et al, 2021; Figure 1). Exosomes' functions encompass an elaborative list depending on the origin of cell/tissue.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Derived Tailored Exosomes Treat Bacteria-Associated Diabetes Foot Ulcers: A Customized Approach From Bench to Bed

et al. 2021

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Exosomes are nano-vesicles of endosomal origin inherited with characteristics of drug delivery and cargo loading. Exosomes offer a diverse range of opportunities that can be exploited in the treatment of various diseases post-functionalization. This membrane engineering is recently being used in the management of bacteria-associated diabetic foot ulcers (DFUs). Diabetes mellitus (DM) is among the most crippling disease of society with a large share of its imposing economic burden. DM in a chronic state is associated with the development of micro- and macrovascular complications. DFU is among the diabetic microvascular complications with the consequent occurrence of diabetic peripheral neuropathy. Mesenchymal stromal cell (MSC)-derived exosomes post-tailoring hold promise to accelerate the diabetic wound repair in DFU associated with bacterial inhabitant. These exosomes promote the antibacterial properties with regenerative activity by loading bioactive molecules like growth factors, nucleic acids, and proteins, and non-bioactive substances like antibiotics. Functionalization of MSC-derived exosomes is mediated by various physical, chemical, and biological processes that effectively load the desired cargo into the exosomes for targeted delivery at specific bacterial DFUs and wound. The present study focused on the application of the cargo-loaded exosomes in the treatment of DFU and also emphasizes the different approaches for loading the desired cargo/drug inside exosomes. However, more studies and clinical trials are needed in the domain to explore this membrane engineering.

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“…In studying these oligonucleotide therapeutics, researchers simultaneously work to overcome challenges that occur in treatments such as non-specific delivery of therapeutic RNAs, stimulation of immunogenicity by delivered RNAs or its carriers, risk of degradation by extracellular nucleases, or finding a suitable vector to deliver the therapeutic agent [69,70,73]. One possible solution to that problem seems to be employing exosomes as carriers of therapeutic factors [64,[74][75][76][77]. Exosomes were reported to effectively deliver therapeutic cargo for cancer treatment [70,77], neurodegenerative diseases [65,78] and virus infections including COVID-19 [79,80].…”

Section: Potential Medical Applications Of Functional Rna Aptamers (Frnaa)mentioning

confidence: 99%

Role of RNA Motifs in RNA Interaction with Membrane Lipid Rafts: Implications for Therapeutic Applications of Exosomal RNAs

Mańka

Janas

Sapoń

et al. 2021

IJMS

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RNA motifs may promote interactions with exosomes (EXO-motifs) and lipid rafts (RAFT-motifs) that are enriched in exosomal membranes. These interactions can promote selective RNA loading into exosomes. We quantified the affinity between RNA aptamers containing various EXO- and RAFT-motifs and membrane lipid rafts in a liposome model of exosomes by determining the dissociation constants. Analysis of the secondary structure of RNA molecules provided data about the possible location of EXO- and RAFT-motifs within the RNA structure. The affinity of RNAs containing RAFT-motifs (UUGU, UCCC, CUCC, CCCU) and some EXO-motifs (CCCU, UCCU) to rafted liposomes is higher in comparison to aptamers without these motifs, suggesting direct RNA-exosome interaction. We have confirmed these results through the determination of the dissociation constant values of exosome-RNA aptamer complexes. RNAs containing EXO-motifs GGAG or UGAG have substantially lower affinity to lipid rafts, suggesting indirect RNA-exosome interaction via RNA binding proteins. Bioinformatics analysis revealed RNA aptamers containing both raft- and miRNA-binding motifs and involvement of raft-binding motifs UCCCU and CUCCC. A strategy is proposed for using functional RNA aptamers (fRNAa) containing both RAFT-motif and a therapeutic motif (e.g., miRNA inhibitor) to selectively introduce RNAs into exosomes for fRNAa delivery to target cells for personalized therapy.

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Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development

Cited by 28 publications

References 247 publications

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

Mesenchymal Stromal Cell-Derived Tailored Exosomes Treat Bacteria-Associated Diabetes Foot Ulcers: A Customized Approach From Bench to Bed

Role of RNA Motifs in RNA Interaction with Membrane Lipid Rafts: Implications for Therapeutic Applications of Exosomal RNAs

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