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Review
. 2022 Nov 22;16(11):17802-17846.
doi: 10.1021/acsnano.2c08774. Epub 2022 Nov 10.

Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

Rumiana Tenchov  1 , Janet M Sasso  1 , Xinmei Wang  1 , Wen-Shing Liaw  1 , Chun-An Chen  1 , Qiongqiong Angela Zhou  1
Affiliations
Review

Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

Rumiana Tenchov et al. ACS Nano. .

Abstract

Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties─innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity─allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.

Keywords: biomarker; blood−brain barrier; diagnostics; drug delivery; exosome; extracellular vesicle; nanocarrier; nanoparticle; therapeutics.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Scheme of exosome biogenesis and secretion. The inset exemplifies the molecular constituents of the exosomes.
Figure 2
Figure 2
Publication trends of exosomes and lipid nanoparticles applied to drug delivery. (A) Comparison of the trends in the number of publications related to exosomes and lipid nanoparticles. The number of publications has been estimated by combining drug-delivery-related search terms such as “drug delivery”, “pharmaceutic”, and “carrier” with the terms “lipid nanoparticle” vs “exosome” or “extracellular vesicle”. (B) Corresponding yearly percentages of publications related to exosomes (EX) and lipid nanoparticles (LNP) in journal articles (JRN) and patents (PAT) calculated for each specific year are compared.
Figure 3
Figure 3
Timeline of major research and development milestones related to exosomes and their medical applications.,,−
Figure 4
Figure 4
Journal and patent publication trends of exosome research in drug delivery and diagnostics and the association with research funding. (A) Trends in the number of publications related to exosomes in drug delivery and diagnostics, including journal articles and patents. (B) Number of documents originating from organizations in the USA as correlated with the annual NIH funding.
Figure 5
Figure 5
Top countries publishing journal articles (A) and patents (B) related to exosomes in drug delivery and diagnostics.
Figure 6
Figure 6
Top patent assignees from companies (A) and universities and hospitals (B) for patents related to exosome applications in drug delivery and diagnostics.
Figure 7
Figure 7
Top patent offices receiving patent applications for exosomes in drug delivery and diagnostics.
Figure 8
Figure 8
Flow of patent filings related to exosome applications in therapy and diagnostics from different patent assignee locations (left) to various patent offices of filing (right). The abbreviations on the right indicate the patent offices of China (CN), United States (US), Canada (CA), Australia (AU), World Intellectual Property Organization (WO), Great Britain (GB), Brazil (BR), European Patent Office (EP), India (IN), Israel (IL), Spain (ES), Japan (JP), Germany (DE), Russian Federation (RU), Korea (KR), France (FR), and Turkey (TR).
Figure 9
Figure 9
Key concepts in the scientific publications relevant to the exosome applications in drug delivery and diagnostics. (A) Number of publications exploring key concepts related to exosome applications in therapy and diagnostics. (B) Trends in key concepts presented in the articles related to exosome applications in therapy and diagnostics during the years 2017–2021.
Figure 10
Figure 10
Representative molecular structures of the major lipid classes in exosomes.
Figure 11
Figure 11
Number of documents mentioning specific types of lipids related to exosome applications in therapeutics and diagnostics. (A) A top list of classes of lipids with the numbers of associated documents. (B) Annual growth of document numbers.
Figure 12
Figure 12
Number of documents concerning major exosome proteins in the documents related to exosome applications in therapeutics and diagnostics.
Figure 13
Figure 13
Types of RNA molecules in exosome applications and their document counts. (A) Distribution of the number of documents related to exosome applications in therapy and diagnostics concerning various RNAs during the years 2012–2021. (B) Annual trends in the number of the same documents. (Percentages are calculated with yearly publication numbers for each RNA, normalized by the total number of publications for the same RNA in the same time period.)
Figure 14
Figure 14
Trends in the number of documents related to exosome applications in therapeutics and diagnostics concerning various exosome isolation methods during the years 2014–2021. (Percentages have been calculated with yearly publication numbers for each isolation method, normalized by the total number of publications for the same isolation method in the same time period.)
Figure 15
Figure 15
Percentages of documents related to exosome applications in therapy and diagnostics concerning various exosome loading methods.
Figure 16
Figure 16
Correlation between exosome donor cells and the diseases to which the exosomes have been applied to in the studies related to exosomes in therapy and diagnostics, as represented by the number of documents in the CAS Content Collection.
Figure 17
Figure 17
Distribution of the publications in the CAS Content Collection related to exosome applications in therapy and diagnostics with respect to the target diseases.
Figure 18
Figure 18
Diagnostic vs therapeutic applications of exosomes. (A) Comparison of the number of documents related to exosome applications in therapy vs diagnostics. Inset: Annual growth of the number of documents related to exosome applications in therapy vs diagnostics. (B) Comparison of the number of documents related to exosome applications in therapy vs diagnostics with respect to their role indicators (THU, therapeutic; DGN, diagnostic).
Figure 19
Figure 19
Promising exosome therapeutic companies and targeted diseases.
See this image and copyright information in PMC

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