Sage Journals: Discover world-class research

Abstract

The lung is a vital organ in the respiratory system, and there is a critical need to develop more effective methods for lung health management. Extracellular vesicles (EVs) play an important role in intercellular communication. They exhibit high bioavailability and low immunogenicity, making them essential in maintaining cellular homeostasis and in the prevention and treatment of numerous diseases. This review describes the diverse sources, isolation techniques, functions, and challenges associated with EVs, particularly exosomes. We highlight their significant role in the diagnosis and treatment of lung diseases, as well as their potential as drug delivery vehicles. By synthesizing recent advances in EVs research, this review aims to provide a theoretical foundation for future studies and clinical applications of EVs.

Graphical Abstract

Keywords

extracellular vesicles lung diseases diagnosis treatment drug delivery

Introduction

The lung works around the clock in our bodies, providing the most basic oxygen support for life and ensuring that the organism functions normally. However, lung health is at risk due to air pollution, particularly from vehicle and industrial exhaust. Lung cancer and chronic obstructive pulmonary diseases (COPD) are more common in smokers, and secondhand smoke as a risk factor, elevates the incidence of respiratory illnesses in family members^1,2. Concern over lung health has grown steadily in the last few years. The focus has shifted from seeking medical attention after the onset of disease to preventing lung diseases and managing lung health every day. Consequently, the pressing need for a healthy lifestyle is driving up demand for the creation and use of innovative technologies.

Extracellular vesicles (EVs), which serve as carriers for intercellular substance and information transfer, offer novel opportunities for diagnosing and treating lung diseases³. Secreted by all cell types, EVs are classified into exosomes, microvesicles, and apoptotic bodies based on their size, biogenesis, and secretion mechanisms^4,5. Exosomes are formed through the endosome system and have a size range of 30-150nm. Microvesicles are directly generated by the budding of the plasma membrane, with a size range of 100-1000nm. Apoptotic bodies are produced by membrane blebbing during the late stage of apoptosis, and their size is generally larger than 1000nm. The 2023 updated guidelines from the International Society for Extracellular Vesicles (ISEV) recommend using “extracellular vesicle” as a generic term for vesicles of all sizes⁴. This recommendation is due to the difficulty in enriching EVs produced by different mechanisms, the lack of definitive characterization of biogenesis-based subtypes, and the absence of universal molecular markers for each EV subtype.

These EVs selectively encapsulate active substances such as proteins and nucleic acids, which regulate physiological and pathological processes^5,6. EVs retain the properties of parent cells, so the characteristics of EVs from various sources are significantly different. To advance biomedical technology and improve human health, it is essential to summarize recent progress in EVs research and develop innovative therapeutic strategies for lung diseases. This article reviews EVs isolation methods and related clinical trials, while also highlighting the latest advances in EV-based diagnostics and therapeutics for pulmonary diseases.

EVs from different sources

EVs derived from mesenchymal stem cells

It is well known that mesenchymal stem cells (MSCs) stimulate immuno-modulation and tissue regeneration⁷. Mesenchymal stem cell–derived EVs (MSC-EVs), especially exosomes (MSC-Exos), have high bioavailability and low immunogenicity^8–10. According to studies, paracrine processes including the release of exosomes by MSCs may be related to the therapeutic benefits of MSCs. The potential application of MSC-EVs for different tissue repair and regeneration has been assessed in an increasing number of research^8–10, and it is becoming a growing trend as an appropriate replacement for stem cell therapy¹¹.

The therapeutic efficacy of MSC-EVs is exerted by tissue regeneration, repair of damaged tissues, and immunomodulation. Studies demonstrate that MSC-Exos exhibit potent wound-healing and angiogenesis-promoting functions, and show an effective anti-scar formation and anti-inflammatory effects¹². Additionally, MSC-Exos modulate macrophage polarization, decreasing pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ, G-CSF) and enhancing anti-inflammatory cytokines (IL-4, IL-10)¹³. In a rat model of acute graft versus host disease (aGVHD), MSC-Exos reduced the CD4⁺/CD8⁺ T-cell ratio, increased Treg cells, and decreased autophagy in the spleen and thymus¹⁴.

EVs derived from immune cells

Beyond MSC-derived EVs, immune cell-derived EVs also demonstrate therapeutic potential. They have become powerful immune response stimulators as well as potential cancer treatment medications. Dendritic cell-derived exosomes (DC-Exos) include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule¹⁵. DC-Exos have the potential to promote immune cell-dependent tumor rejection^16,17. Evidence suggests that DC-Exos enhance anti-tumor immunity of NK cells in patients with advanced nonsmall cell lung cancer (NSCLC)¹⁸.

Recent studies have explored the role of other immune cell-derived EVs. Jung et al.¹⁹ used engineered Jurkat T-cells expressing IL-2 at the plasma membrane to create IL-2-sEVs, which increased the anti-cancer ability of CD8⁺ T-cells without affecting regulatory Treg cells and down-regulated cellular and exosomal PD-L1 expression in melanoma cells, causing their increased sensitivity to CD8⁺ T-cell-mediated cytotoxicity. Exosomes derived from NK cells have lower immunogenicity and greater stability, and they also possess antitumor properties²⁰. Kang et al.²¹ demonstrated that NK-exosomes exhibit cytotoxic effects on circulating tumor cells, suggesting their potential in NSCLC therapy.

EVs from other sources

In addition to MSC-EVs and immune cell EVs, EVs from other sources have also been further investigated. Yan et al.²² demonstrated miR-31-5p delivered by milk exosomes accelerating diabetic wound healing through promoting angiogenesis. Zhou et al.²³ identified plasma-derived exosomal miR-15a-5p has the potential as a biomarker for early endometrial cancer detection. Not only can EVs be secreted by animal cells, plant cells can also secrete EVs²⁴. Plant-derived EVs, as active ingredients of natural origin, have shown high advantages in terms of safety and functionality²⁵. EVs derived from ginger can improve intestinal inflammation by modulating intestinal flora and increasing the release of anti-inflammatory factors²⁶. Over the years, the research on plant-derived EVs such as ginseng and grape has attracted increasing attention, but the secretion mechanism and identification of plant-derived exosomes still need to be further explored.

EVs isolation methods

EVs are a promising field of research and have wide implications for the diagnosis, treatment and drug delivery of human diseases. Generally, EVs isolation is based on biophysical characteristics such as the size, density, charge and surface composition of EVs. Each method has its own advantages and disadvantages^27,28. The increasing amount of research on EVs indicates that finding a more efficient and high-yield method of extracting them is crucial to developing the study and use of EVs-related medications. Table 1 lists the most common techniques for isolating EVs. With the continuous progress of technology, it is believed that there will be more efficient and convenient methods to obtain EVs in the future.

Table 1.

EVs isolation methods.

Isolation methods	Principle	Advantage	Disadvantage	Reference
Ultracentrifugation	Particle size, density, sedimentation coefficient	Low cost, purity, high recovery rate	High cost, damage exosomes, unsuitable for diagnosis	Patel et al.²⁹
Size-exclusion chromatography	Particle size	High purity, scalability, functionality of exosomes	Low purity and specificity	Stranska et al.³⁰
Polymer precipitation	Solubility, surface charge	Easy operation, high efficiency, low cost	Low purity and specificity, low specificity	Martínez-Greene et al.³¹
Immunoaffinity	Specific binding of antibodies to exosome markers	High purity, specificity	Low production, high cost, poor scalability	Ueda et al.³²
Microfluidics	Particle size, biological properties	Efficient, high purity, specificity	Low production, high cost, limited scalability, complex instrumentation	Hao et al.³³

Role of EVs in lung disease

EVs in lung disease diagnosis

Investigating particular biomarkers and novel treatment strategies in lung diseases is urgently needed because lung diseases have emerged as a major health concern. Currently, EVs, particularly exosomes, have achieved significant breakthroughs in early disease detection and prognostic diagnosis^34–36. EVs can be readily detected in various physiological fluids including blood, saliva, and urine. As illustrated in Fig. 1, the diverse contents of EVs are being actively explored for pulmonary disease diagnostics.

Figure 1.

EVs as diagnostic (BALF: bronchoalveolar lavage fluid).

The level of gene expression in EVs offers a novel biomarker for lung disease diagnosis and progression. Gan et al.³⁷ reported eleven dysregulated exosomal circRNAs from the blood of idiopathic pulmonary fibrosis (IPF) patients, with significant increases in three circRNAs in IPF patients. Vázquez-Mera et al.³⁸ assessed microRNAs (miRNAs) profiles in serum exosomes of asthma patients and identified immune-related miRNAs (miR-21-5p, miR-126-3p, miR-146a-5p, miR-215-5p), which can be used as asthma phenotype/ endogenous and severity clinically relevant noninvasive biomarkers. Kaur et al.³⁹ identified that miR-122-5p was down-regulated three- to five-fold in lung-tissue-derived exosomes of COPD patients as compared to healthy nonsmokers and smokers, respectively. Sundar et al.⁴⁰ demonstrated that plasma-derived EVs miRNA-based molecular analysis hold significant potential for use in the development of biomarkers for the diagnosis, prognosis, and treatment of COPD. Furthermore, EVs-associated proteins also play a critical role for lung disease diagnosis. Enomoto et al.⁴¹ identified surfactant-associated protein B (SFTPB) in serum EVs as a potential biomarker for progressive pulmonary fibrosis.

Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases¹. NSCLC and small cell lung cancer (SCLC) are the two primary types into which lung cancer can be generally divided from a histological and therapeutic standpoint⁴². Current and previous smoking, passive smoking, occupational exposure, and chronic obstructive pulmonary disease or pulmonary fibrosis are the primary risk factors for lung cancer⁴³. Apart from low-dose spiral CT scanning, there is no effective technique for early detection of lung cancer.

Exosomal nucleic acids such as tRNAs, mRNAs, miRNAs, and long noncoding RNAs (LncRNAs) have been the subject of an increasing number of in recent years⁴⁴. miRNAs play a significant role in the posttranscriptional control of biological processes. Cazzoli et al.⁴⁵ studied exosomes extracted from the blood of lung adenocarcinoma patients and found that the expression levels of four miRNAs carried by exosomes were higher than those of healthy smokers. It was discovered that exosomes from recurring tumors had significantly higher levels of miR-21 and miR-155, indicating that alterations in exosomal miRNAs might accurately reflect the clinical characteristics of lung cancer⁴⁶. The proteins and DNA of EVs have been evaluated by an increasing number of researchers as potential diagnostic biomarkers for non-small cell lung cancer^47,48. Through investigations of exosomal proteins, Sandfeld-Paulsen et al.⁴⁹ discovered that the exosomes of CD151, CD171, and tetraspanin eight differed significantly between the histological subtypes of cancer patients and noncancer patients. Studies have shown that estimated glomerular filtration rate (EGFR) mutation analysis of bronchoalveolar lavage fluid (BALF) or plasma EVs can obtain accurate, specific and rapid results^50,51. To improve the prognosis of patients with lung cancer, further research into biomarkers and novel treatments is necessary.

EVs treatment of lung disease

EVs exhibit special benefits when used to treat lung diseases. In addition to lung diseases such as lung cancer and COPD, a large number of patients are also suffering from diseases like pulmonary fibrosis, interstitial pneumonia, and asthma. With age, the declining regenerative capacity of cells slows down lung injury repair^52,53.

Mesenchymal stem cell–derived EVs have beneficial effects in the treatment of lung injury. The potential mechanisms of MSC-EVs in reducing lung injury have been investigated in many studies (Fig. 2). Studies have shown that MSC-Exos can regulate macrophage immune function, reduce pulmonary fibrosis and improve pulmonary hypertension in experimental mice^54,55. Xu et al.⁵⁶ showed that MSC-Exos prevented excessive collagen formation and extracellular matrix deposition in the lungs by inhibiting the expression of TGF-β1, connective tissue growth factor (CTGF), and COL1A1 genes in fibroblasts via Let-7i-5p. Liu et al.⁵⁷ delivered miR-17-5p to receptor cells, via exosomes from human embryonic stem cells to target platelet-responsive protein-2 (Thbs2) to prevent pulmonary fibrosis. In addition, MSC-Exos can improve fibrosis by regulating fibroblast differentiation, as well as inducing apoptosis and senescence in fibroblasts and myofibroblasts⁵⁸. Compared with cell therapy, MSC-EVs have a more flexible mode of drug delivery, and the use of nebulization enables the therapeutic drugs to reach the airways or lungs directly, requiring a smaller dose. In preclinical lung damage models, researchers present the biological distribution and effects of nebulized cells-derived extracellular vesicles (Hamsc-EVs) and examine the safety of nebulized administration⁵⁹.

Figure 2.

Mechanisms of MSC-EVs treat lung injury: (a) Nebulization is used to transfer EVs to the lungs for healing; (b) EVs enter target cells by three primary pathways: direct membrane fusion, receptor-mediated endocytosis, and direct endocytosis; (c) MSC-EVs are involved in the treatment of lung diseases via related signaling pathways^54–57. A downward arrow indicates inhibition of the signal pathway, while an upward arrow indicates activation of the signal pathway; (d) EVs can attenuate the early inflammatory response by reducing the inflammatory response, differentiating macrophages from a pro-inflammatory M1 phenotype to an inhibitory inflammatory M2 phenotype, and reducing inflammatory cytokine release^54,55; (e) EVs reduce lung fibrosis by inhibiting myofibroblast differentiation⁵⁶; (f) EVs deliver miR and protein to other receptor cells, such as alveolar epithelial cells.⁵⁸

In addition, other types of vesicles have been actively studied in the treatment and prevention of lung diseases. Human bronchial epithelial cell-derived EVs were found to treat pulmonary fibrosis and lung epithelial cell senescence by inhibiting TGF-β-WNT crosstalk⁶⁰. Fibroblast exosome-derived microRNA-22 regulates fibroblast differentiation to myofibroblasts to ameliorate fibrosis through the ERK1/2 pathway by inhibiting TGF-β1 induced α-SMA expression⁶¹. Analysis showed that inhalation of lung spheroid cell secretome (LSC-Sec) and exosomes (LSC-Exo) could reestablish normal alveolar structure, reduce collagen accumulation and myofibroblast proliferation to attenuate and resolve pulmonary fibrosis⁶². Previous studies demonstrated that ACE2-expressing human LSC-Exo could function as a prophylactic therapy to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection⁶³. Zhou et al.⁶⁴ found that endothelial progenitor cell exosomes carrying miR-126-3p and miR-126-5p could increase the expression of tight junction proteins and maintain the integrity of the alveolar epithelial barrier. Recent studies have revealed that M2-like macrophage-derived EVs play a protective role in the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), partly mediated by miR-709⁶⁵. This offers a potential strategy for assessing disease severity and treating ALI/ARDS. With the discovery of increasingly diverse EVs functions, it provides more possibilities for the application of EVs in the treatment of lung diseases. Table 2 collects some of the studies on EVs in the therapeutic field of lung disease.

Table 2.

Applications of EVs in lung diseases.

Disease	Source	Model	MiRNA/proteins	Dosage	Administration routes	Treatment	Reference
Pulmonary fibrosis	Umbilical cord mesenchymal stromal cells–derived EVs	Bleomycin induced mouse model	miR-21, miR-23	20 μg in 100 μl of PBS	Intravenous injection	Intravenous injection on days 7 and 21; euthanized on day 35	Shi et al.⁶⁶
IPF	Human bronchial epithelial cell–derived EVs	Bleomycin induced mouse model	miR-16, miR-26a, miR-26b, miR-141, miR-148a, miR-200a	2.0 × 10⁹ particles/body	Intratracheal administration	Intratracheally on day 7 and day 14	Kadota et al.⁶⁷
Bacterial pneumonia	Mesenchymal stem (stromal) cells microvesicles	E.coli Pneumonia–induced ALI in Mice	/	Instilled intratracheally (30 or 60 μl) or injected intravenously (90 μl)	Instilled intratracheally or injected intravenously	Administer the drug once; mice were killed at 18, 24, or 72 h	Monsel et al.⁶⁸
ALI	Mesenchymal stem cell–derived extracellular vesicles	Lipopolysaccharide-induced lung injury	miR-27a-3p	50 µg/mice	Administered via the tail veins; intratracheal administration	Analysis after 48 h	Wang et al.⁶⁹
Lung injury	Adipose mesenchymal stem cells extracellular vesicles	Rat (PM2.5, 100 μl, 5 mg/ml)or cell (PM2.5, 50 μg/ml) models	/	3 × 1010 particles in 50 μl PBS	Intratracheal administration	Analysis after 24 h	Gao et al.⁷⁰
Chronic asthma	hUCMSCs cultured under hypoxic-derived EVs	Ovalbumin-induced asthmatic mice	CAV-1 protein	40 μg Hypo-Evs (suspended in 0.5 ml PBS)	Nebulization	Administration was carried out on the 26th, 33th, 40th and 47th days	Luo et al.⁷¹

Researchers and entrepreneurs have been tremendously excited about the development of EVs. There are already a variety of EVs-related clinical trials available on the ClinicalTrials.gov website, including several research initiatives on therapies for conditions including acute respiratory distress syndrome (ARDS), COVID-19, and cancer. Table 3 provides clinical research information on EVs used in the treatment of lung cancer, ARDS, COVID-19, and other illnesses. EVs-related treatment has been shown to be safe and effective in several of research fields.

Table 3.

Clinical applications of EVs in lung diseases.

Name	Status	Condition	Type of EVs	Location	NCT number
A Clinical Study of Mesenchymal Progenitor Cell Exosomes Nebulizer for the Treatment of Pulmonary Infections	phase 1/2	Drug-resistant	MSC-/progenitor-cell-derived exosomes	Shanghai, China	NCT04544215
A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes for the Treatment of Severe Novel Coronavirus Pneumonia	Completed; phase 1	SARS-CoV-2 pneumonia	MSC-derived exosomes	Shanghai, China	NCT04276987
A Tolerance Clinical Study on Aerosol Inhalation of Mesenchymal Stem Cells Exosomes in Healthy Volunteers	Completed; phase 1	Safety and tolerance studies	MSC-derived exosomes	Shanghai, China	NCT04313647
A Clinical Study of Mesenchymal Stem Cell Exosomes Nebulizer for the Treatment of ARDS	phase 1/2	Acute respiratory distress syndrome	Allogeneic human MSC-derived exosomes	Ruijin, China	NCT04602104
Evaluation of Safety and Efficiency of Exosome Inhalation In SARS-CoV-2 Associated Pneumonia	Completed; phase 1/2	SARS-CoV-2 pneumonia	MSC-derived exosomes	Samara, Russia	NCT04491240
Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Pneumonia	phase 2	SARS-CoV-2 pneumonia	MSC-derived exosomes	Samara, Russia	NCT04602442
COVID-19 Specific T-Cell-Derived Exosomes	phase 1	SARS-CoV-2 pneumonia	T-cell-derived exosomes	Kayseri, Turkey	NCT04389385
Extracellular Vesicle Infusion Therapy for Severe COVID-19	Completed; phase 2	SARS-CoV-2 pneumonia, acute respiratory distress syndrome	Bone-marrow-derived EVs	United States	NCT04493242
Trial of a Vaccination with Tumor Antigen-loaded Dendritic Cell-derived Exosomes	Completed; phase 2	Non-small-cell lung cancer	Dendritic-cell-derived exosomes loaded with antigen	Villejuif, France	NCT01159288
Evaluation of the Safety of CD24-Exosomes in Patients With COVID-19 Infection	Unknown status	SARS-CoV-2	CD24-exosomes derived from engineered 293 cells	Tel Aviv, Israel	NCT04747574

Nanotechnology-based drug delivery systems provide a promising strategy for the targeted delivery of traditional chemical drugs and novel small molecule therapeutic agents to treat lung disease⁷². Various nanomaterials such as lipid nanoparticles and polymer nanoparticles have been applied in drug delivery, but these delivery mechanisms all have their own limitations^73,74. Because of their small size, excellent safety, and ability to cross physiological barriers, EVs are considered to be a more effective drug delivery vehicles. EVs may carry a variety of medications, mostly small molecule medication (doxorubicin, curcumin, etc), protein medications (enzymes, transmembrane proteins, etc), and nucleic acid medications (miRNA, siRNA, etc)⁷⁵. There are two main approaches for loading drug compounds into EVs: exogenous loading (postloading) and endogenous loading (preloading)⁷⁶. Several drug loading strategies were compiled in Table 4. Wang et al.⁷⁷ used a simple slight sonication method to prepare PTX-M1-Exos delivery system, polarized M1 macrophage exosomes, which enhanced paclitaxel (PTX) anti-tumor effects. Zheng et al.⁷⁸ designed CAR-T-cell-derived exosome-encapsulated paclitaxel (PTX@CAR-Exos) for the treatment of a mouse model of lung cancer, and inhalation of PTX@CAR-Exos accumulated within the tumor region and reduced the tumor size. RuizdelRio et al.⁷⁹ demonstrated that fibroblast-derived EVs encapsulating the drug reduced fibrosis in profibrotic fibroblasts in vitro and also reached the fibrotic heart and lungs in vivo, improving the biodistribution of the free drugs. Exosome membrane of M2 macrophages and poly(lactic-co-glycollic) acid nanoparticles (PLGA NPs) wrapped with the smart silencer of Dnmt3aos were synthesized to treat asthma mice, which was followed by the investigation of therapeutic outcomes and the mechanism in vivo⁸⁰. Wang et al.⁸¹ explored M2 macrophage-derived exosomes as carriers for targeted antibiotic delivery (Antibiotics@Exos) have been used to optimize treatment strategies for bacterial pneumonia.

Table 4.

Different techniques for drug loading.

Method	Advantage	Disadvantage	Detailed method	Reference
Preloading approaches	The integrity and function of EVs are preserved	Complex operation, high cost	Co-incubation	Pascucci et al.⁸²
Preloading approaches	The integrity and function of EVs are preserved	Complex operation, high cost	Genetic engineering	Fu et al.⁸³
Postloading approaches	Preparation is simple	Damage EVs integrity, additional purification steps are required to remove the unloaded drug	Incubation	Kannavou et al.⁸⁴
			Freezing and thawing cycle	Kannavou et al.⁸⁴
			Membrane permeation incubation (saponin)	Haney et al.⁸⁵
			Chemical transfection	Shtam et al.⁸⁶
			Electroporation	Liu et al.⁸⁷
			Ultrasonic treatment	Liu et al.⁸⁷

EVs are being researched more and more as a means for carrying nucleic acids⁸⁸. Liu et al.⁸⁷ loaded IL-12 mRNA into human embryonic kidney cell-derived exosomes (HEK-Exo) by electroporation, generating loaded IL-12 mRNA exosomes (IL-12-Exo). Research conducted on mouse models of lung cancer has demonstrated that IL-12-Exo has a lower systemic toxicity and a better biological distribution in the lung cancer tumor microenvironment following inhalation administration than liposomes loaded with IL-12 mRNA (IL-12-Lipo)⁸⁷.

EVs that have been preloaded in vivo can be offered targeted, unique cellular regulatory, and drug-therapeutic properties. Research has demonstrated that tLyP-1 exosome can transport siRNA to human non-small cell lung cancer cells⁸⁹. Zhang et al.⁹⁰ developed an engineered MSC-Exos with SARS-CoV-2-S-RBD- and miR-486-5p- modification that suppressed ferroptosis and fibrosis of MLE-12 cells in vitro, and alleviated RILI and long-term RIPF in ACE2 humanized mice in vivo. The use of EVs as delivery vehicles has several benefits, but there are still many obstacles to overcome, such as increasing drug loading effectiveness and precisely locating cells and tissues in vivo. Since the current technical conditions are limiting, novel technologies are critically needed to solve these challenges^91,92.

Prospect

Many breakthroughs have been made in the study of EVs, especially in the field of drug delivery, regeneration and tissue repair, and specific biomarkers for diagnosis. The introduction of in vitro diagnostic products based on EVs technology further proves the development potential of EVs in the field of diagnosis. It is expected that in the foreseeable future, the diagnosis area will continue to be the main exhibition area for EVs products. Although impressive findings have been made in the study of EVs, there are still obstacles to industrial transformation. For example, rapid clearance of EVs in vivo will limit the long-term therapeutic effects. Another challenge in the industrialization of EVs is the nonuniformity caused by various cell culture conditions and cell passage. Therefore, standardized protocols for the isolation and characterization of EVs are urgently needed.

EVs can be delivered to the target organs for treatment more efficiently by atomized inhalation, nasal drops and other drug delivery technologies. The application field of EVs will be further expanded by combining with a series of biomaterials. In addition, EVs are easy to be engineered, and the function of active targeting can be realized by adding targeting molecules. These advantages expand the potential of drug delivery from EVs. With the development of cell manipulation and bioengineering technology, engineering modification can highlight the best characteristics of EVs as vehicles, and might eventually become the mainstream trend. Notably, one pressing issue that engineered EVs must address is targeted specificity.

EVs have shown significant promise for use in the three main domains including diagnostic, treatment, and drug deliveries. It is anticipated that researchers will maintain their passion for this area of study and actively investigate the field of plant-derived EVs and engineered EVs. However, close integration with other emerging technologies is necessary for the development of EVs in the future. Examples include (1) combining microfluidic methods for effective enrichment; (2) using artificial intelligence for intelligent analysis; and (3) combining with biomaterials to achieve sustained release and regulation. In the future, only by strategically integrating other technologies and continuously overcoming challenges can the advantages of EVs be fully realized.

Footnotes

Acknowledgements

The authors thank ANEXT Shanghai Biotechnology Co., Ltd, and Oriental Beauty Valley Institute of Regenerative Medicine for continuous support of this work. All the figures in the manuscript were drawn in Figdraw. The authors thank their colleagues for helpful suggestions.

ORCID iD

Weiwei Wang

Ethical Considerations

Not applicable.

Statement of Human and Animal Rights

This article does not contain any studies with human or animal subjects.

Statement of Informed Consent

Not applicable.

Author Contributions

Wang J: manuscript writing, collection of data; Shi YN: manuscript writing, collection of data; Su YH: manuscript writing, creation of figures; Pang CY: manuscript writing; Yang YM: manuscript writing; Wang WW: conception and design, manuscript writing, collection of data, interpretation of data.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

Bray

Laversanne

Sung

Ferlay

Siegel

Soerjomataram

Jemal

. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.

Agustí

Celli

Criner

Halpin

Anzueto

Barnes

Bourbeau

Han

Martinez

Montes

Oca

Mortimer

, et al. Global initiative for chronic obstructive lung disease 2023 report: GOLD executive summary. Eur Respir J. 2023;61(4):2300239.

Kadota

Fujita

Araya

Ochiya

Kuwano

. Extracellular vesicle-mediated cellular crosstalk in lung repair, remodelling and regeneration. Eur Respir Rev. 2022;31(163):210106.

Welsh

Goberdhan

DCI

O’Driscoll

Buzas

Blenkiron

Bussolati

Cai

Di Vizio

Driedonks

TAP

Erdbrügger

Falcon-Perez

, et al. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13(2):e12404.

Pegtel

Gould

. Exosomes. Annu Rev Biochem. 2019;88:487–514.

Valadi

Ekström

Bossios

Sjöstrand

Lee

Lötvall

. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–59.

Maldonado

Patel

Smith

Barnes

Gustafson

Rao

Samsonraj

. Clinical utility of mesenchymal stem/stromal cells in regenerative medicine and cellular therapy. J Biol Eng. 2023;17(1):44.

Levy

Abadchi

Shababi

Ravari

Pirolli

Bergeron

Obiorah

Mokhtari-Esbuie

Gheshlaghi

Abraham

Smith

, et al. Induced pluripotent stem cell-derived extracellular vesicles promote wound repair in a diabetic mouse model via an anti-inflammatory immunomodulatory mechanism. Adv Healthc Mater. 2023;12(26):e2300879.

Zheng

Bian

Qiu

Bishop

Wan

Sun

Sequeira

Atala

Zhao

. Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis. Inflamm Regen. 2023;43(1):47.

10.

Xie

Song

Dai

Cui

Tang

Chang

Wang

Gao

, et al. Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease: a phase I/II clinical trial. Gen Psychiatr. 2023;36(5):e101143.

11.

Matsuzaka

Yashiro

. Therapeutic strategy of mesenchymal-stem-cell-derived extracellular vesicles as regenerative medicine. Int J Mol Sci. 2022;23(12):6480.

12.

Xiang

Ding

Qian

Sun

Lee

Zhao

Sun

Zhao

. Exosomes derived from minor salivary gland mesenchymal stem cells: a promising novel exosome exhibiting pro-angiogenic and wound healing effects similar to those of adipose-derived stem cell exosomes. Stem Cell Res Ther. 2024;15(1):462.

13.

Sun

Huang

Zhang

Duan

Wang

. hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater Sci Eng C Mater Biol Appl. 2018;89:194–204.

14.

Wang

Wei

Chen

Lin

Lai

Ding

Zhang

Zeng

. Bone marrow mesenchymal stem cell-derived exosomes effectively ameliorate the outcomes of rats with acute graft-versus-host disease. FASEB J. 2024;38(13):e23751.

15.

Nikfarjam

Rezaie

Kashanchi

Jafari

. Dexosomes as a cell-free vaccine for cancer immunotherapy. J Exp Clin Cancer Res. 2020;39(1):258.

16.

Gehrmann

Näslund

Hiltbrunner

Larssen

Gabrielsson

. Harnessing the exosome-induced immune response for cancer immunotherapy. Semin Cancer Biol. 2014;28:58–67.

17.

Luo

Chen

. Dendritic cell-derived exosomes in cancer immunotherapy. Pharmaceutics. 2023;15(8):2070.

18.

Besse

Charrier

Lapierre

Dansin

Lantz

Planchard

Le Chevalier

Livartoski

Barlesi

Laplanche

Ploix

, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 2016;5(4):e1071008.

19.

Jung

Shin

Kang

Jung

Ryu

Noh

Choi

Jeong

Lee

Kim

, et al. Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer effects through miRNA delivery. J Extracell Vesicles. 2022;11(12):e12287.

20.

Gao

. Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications. Mol Cancer. 2024;23(1):134.

21.

Kang

Niu

Hadlock

Purcell

Zeinali

Owen

Keshamouni

Reddy

Ramnath

Nagrath

. On-chip biogenesis of circulating NK cell-derived exosomes in non-small cell lung cancer exhibits antitumoral activity. Adv Sci. 2021;8(6):2003747.

22.

Yan

Chen

Wang

Yuan

Kang

Zhang

Machens

Rinkevich

Chen

, et al. Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis. Drug Deliv. 2022;29(1):214–28.

23.

Zhou

Wang

Yang

Pan

Zheng

Zhou

Lei

, et al. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma. Mol Cancer. 2021;20(1):57.

24.

Bai

Liu

Zhang

Qin

Song

Yuan

Huang

. Research status and challenges of plant-derived exosome-like nanoparticles. Biomed Pharmacother. 2024;174:116543.

25.

Zhang

Liu

Liang

Thakur

Liu

Yan

. Plant-derived extracellular vesicles (PDEVs) in nanomedicine for human disease and therapeutic modalities. J Nanobiotechnology. 2023;21(1):114.

26.

Teng

Ren

Sayed

Lei

Kumar

Hutchins

Deng

Luo

Sundaram

, et al. Plant-derived exosomal MicroRNAs shape the gut microbiota. Cell Host Microbe. 2018;24(5):637–652.

27.

Yang

Zhang

Chen

Larcher

Chen

Liu

Zhao

Tran

PHL

, et al. Progress, opportunity, and perspective on exosome isolation: efforts for efficient exosome-based theranostics. Theranostics. 2020;10(8):3684–707.

28.

Lai

Chau

Chen

Hill

Korpany

Liang

Lin

Liu

Lunde

, et al. Exosome processing and characterization approaches for research and technology development. Adv Sci. 2022;9(15):e2103222.

29.

Patel

Khan

Zubair

Srivastava

Khushman

Singh

. Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications. Sci Rep. 2019;9(1):5335.

30.

Stranska

Gysbrechts

Wouters

Vermeersch

Bloch

Dierickx

Andrei

Snoeck

. Comparison of membrane affinity-based method with size-exclusion chromatography for isolation of exosome-like vesicles from human plasma. J Transl Med. 2018;16:1.

31.

Martínez-Greene

Hernández-Ortega

Quiroz-Baez

Resendis-Antonio

Pichardo-Casas

Sinclair

Budnik

Hidalgo-Miranda

Uribe-Querol

Ramos-Godínez

MDP

Martínez-Martínez

. Quantitative proteomic analysis of extracellular vesicle subgroups isolated by an optimized method combining polymer-based precipitation and size exclusion chromatography. J Extracell Vesicles. 2021;10(6):e12087.

32.

Ueda

Ishikawa

Tatsuguchi

Saichi

Fujii

Nakagawa

. Antibody-coupled monolithic silica microtips for high throughput molecular profiling of circulating exosomes. Sci Rep. 2014;4:6232.

33.

Hao

Zhang

Chen

Ren

Guo

Yang

. Mechanical stimulation on a microfluidic device to highly enhance small extracellular vesicle secretion of mesenchymal stem cells. Mater Today Bio. 2022;18:100527.

34.

Heydari

Koohi

Rasouli

Rezaei

Abbasgholinejad

Bekeschus

Doroudian

. Exosomes as rheumatoid arthritis diagnostic biomarkers and therapeutic agents. Vaccines. 2023;11(3):687.

35.

Zanganeh

Abbasgholinejad

Doroudian

Esmaelizad

Farjadian

Benhabbour

. The current landscape of glioblastoma biomarkers in body fluids. Cancers. 2023;15(15):3804.

36.

Rahimian

Najafi

Afzali

Doroudian

. Extracellular vesicles and exosomes: novel insights and perspectives on lung cancer from early detection to targeted treatment. Biomedicines. 2024;12(1):123.

37.

Gan

Song

Gao

Zheng

Wang

Zhang

Zen

Liang

Yan

. Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction. J Transl Med. 2024;22(1):264.

38.

Vázquez-Mera

Martelo-Vidal

Miguéns-Suárez

Saavedra-Nieves

Arias

González-Fernández

Mosteiro-Añón

Corbacho-Abelaira

Blanco-Aparicio

Méndez-Brea

Salgado

, et al. Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity. Allergy. 2023;78(1):141–55.

39.

Kaur

Maremanda

Campos

Chand

Hirani

Haseeb

Rahman

. Distinct exosomal miRNA profiles from BALF and lung tissue of COPD and IPF patients. Int J Mol Sci. 2021;22(21):11830.

40.

Sundar

Rahman

. Small RNA-sequence analysis of plasma-derived extracellular vesicle miRNAs in smokers and patients with chronic obstructive pulmonary disease as circulating biomarkers. J Extracell Vesicles. 2019;8(1):1684816.

41.

Enomoto

Shirai

Takeda

Edahiro

Shichino

Nakayama

Takahashi-Itoh

Noda

Adachi

Kawasaki

Koba

, et al. SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis. JCI Insight. 2024;9(11):e177937.

42.

Megyesfalvi

Gay

Popper

Pirker

Ostoros

Heeke

Lang

Hoetzenecker

Schwendenwein

Boettiger

Bunn

Jr , et al. Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin. 2023;73(6):620–52.

43.

Leiter

Veluswamy

Wisnivesky

. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol. 2023;20(9):624–39.

44.

Wang

Cai

Fang

Zhang

. Exosomes as a new frontier of cancer liquid biopsy. Mol Cancer. 2022;21(1):56.

45.

Cazzoli

Buttitta

Di Nicola

Malatesta

Marchetti

Rom

Pass

. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013;8(9):1156–62.

46.

Munagala

Aqil

Gupta

. Exosomal miRNAs as biomarkers of recurrent lung cancer. Tumour Biol. 2016;37(8):10703–14.

47.

Niu

Song

Wang

Xue

Song

Xie

. Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer. Cancer Sci. 2019;110(1):433–42.

48.

Carreca

Tinnirello

Miceli

Galvano

Gristina

Incorvaia

Pampalone

Taverna

Iannolo

. Extracellular vesicles in lung cancer: implementation in diagnosis and therapeutic perspectives. Cancers. 2024;16(11):1967.

49.

Sandfeld-Paulsen

Jakobsen

Bæk

Folkersen

Rasmussen

Meldgaard

Varming

Jørgensen

Sorensen

. Exosomal proteins as diagnostic biomarkers in lung cancer. J Thorac Oncol. 2016;11(10):1701–10.

50.

Jouida

McCarthy

Fabre

Keane

. Exosomes: a new perspective in EGFR-mutated lung cancer. Cancer Metastasis Rev. 2021;40(2):589–601.

51.

Kim

Hur

Kim

Lee

. Extracellular vesicle-based bronchoalveolar lavage fluid liquid biopsy for EGFR mutation testing in advanced non-squamous NSCLC. Cancers. 2022;14(11):2744.

52.

Kizawa

Araya

Fujita

. Divergent roles of the Hippo pathway in the pathogenesis of idiopathic pulmonary fibrosis: tissue homeostasis and fibrosis. Inflamm Regen. 2023;43(1):45.

53.

Watanabe

Markov

Piseaux Aillon

Soberanes

Runyan

Ren

Grant

Maciel

Abdala-Valencia

Politanska

, et al. Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis. Proc Natl Acad Sci USA. 2021;118(20):e2101100118.

54.

Willis

Fernandez-Gonzalez

Anastas

Vitali

Liu

Ericsson

Kwong

Mitsialis

Kourembanas

. Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation. Am J Respir Crit Care Med. 2018;197(1):104–16.

55.

Liu

Zhang

Liu

Zhang

Wang

Huang

. Human umbilical cord mesenchymal stromal cell-derived exosomes alleviate hypoxia-induced pulmonary arterial hypertension in mice via macrophages. Stem Cells. 2023;28:sxad098.

56.

Hou

Zhao

Wang

Jiang

Zhu

Tian

. Exosomal let-7i-5p from three-dimensional cultured human umbilical cord mesenchymal stem cells inhibits fibroblast activation in silicosis through targeting TGFBR1. Ecotoxicol Environ Saf. 2022;233:113302.

57.

Liu

Song

Zhu

Qiao

Wang

. Exosomal miR-17-5p from human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2. Stem Cell Res Ther. 2023;14(1):234.

58.

Harrell

Djonov

Volarevic

Arsenijevic

Volarevic

. Molecular mechanisms responsible for the therapeutic potential of mesenchymal stem cell-derived exosomes in the treatment of lung fibrosis. Int J Mol Sci. 2024;25(8):4378.

59.

Shi

Yang

Monsel

Yan

Dai

Zhao

Shi

Zhou

Zhu

, et al. Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. J Extracell Vesicles. 2021;10(10):e12134.

60.

Kadota

Fujita

Araya

Watanabe

Fujimoto

Kawamoto

Minagawa

Hara

Ohtsuka

Yamamoto

Kuwano

, et al. Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-β-WNT crosstalk. J Extracell Vesicles. 2021;10(10):e12124.

61.

Kuse

Kamio

Azuma

Matsuda

Inomata

Usuki

Morinaga

Tanaka

Kashiwada

Atsumi

Hayashi

, et al. Exosome-derived microRNA-22 ameliorates pulmonary fibrosis by regulating fibroblast-to-myofibroblast differentiation in vitro and in vivo. J Nippon Med Sch. 2020;87(3):118–28.

62.

Dinh

Paudel

Brochu

Popowski

Gracieux

Cores

Huang

Hensley

Harrell

Vandergriff

George

, et al. Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat Commun. 2020;11(1):1064.

63.

Wang

Popowski

Liu

Zhu

Mei

Dinh

Wang

Cheng

. Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2. Nat Commun. 2024;15(1):2236.

64.

Zhou

Goodwin

Cook

Halushka

Chang

Zingarelli

Fan

. Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury. Crit Care. 2019;23(1):44.

65.

Yang

Huang

Wang

Wen

Bai

Cao

Zhang

Wang

Chen

, et al. Extracellular vesicles derived from M2-like macrophages alleviate acute lung injury in a miR-709-mediated manner. J Extracell Vesicles. 2024;13(4):e12437.

66.

Shi

Ren

Wang

Qin

Zhang

Wang

. Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition. Stem Cell Res Ther. 2021;12(1):230.

67.

Kadota

Fujita

Araya

Watanabe

Fujimoto

Kawamoto

Minagawa

Hara

Ohtsuka

Yamamoto

Kuwano

, et al. Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-β-WNT crosstalk. J Extracell Vesicles. 2021;10(10):e12124.

68.

Monsel

Zhu

Gennai

Hao

Rouby

Rosenzwajg

Matthay

Lee

. Therapeutic effects of human mesenchymal stem cell-derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015;192(3):324–36.

69.

Wang

Huang

Zheng

Qiu

Shu

. Mesenchymal Stem cell-derived extracellular vesicles alleviate acute lung injury via transfer of miR-27a-3p. Crit Care Med. 2020;48(7):e599–610.

70.

Gao

Huang

Lin

Zhao

Liu

Han

Dong

, et al. Adipose mesenchymal stem cell-derived antioxidative extracellular vesicles exhibit anti-oxidative stress and immunomodulatory effects under PM2.5 exposure. Toxicology. 2021;447:152627.

71.

Luo

Wang

Mao

Zheng

Dong

. Nebulization of hypoxic hUCMSC-EVs attenuates airway epithelial barrier defects in chronic asthma mice by transferring CAV-1. Int J Nanomedicine. 2024;19:10941–59.

72.

Doroudian

Azhdari

Goodarzi

O’Sullivan

Donnelly

. Smart nanotherapeutics and lung cancer. Pharmaceutics. 2021;13(11):1972.

73.

Jeppesen

Zhang

Franklin

Coffey

. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol. 2023;33(8):667–81.

74.

Doroudian

MacLoughlin

Poynton

Prina-Mello

Donnelly

. Nanotechnology based therapeutics for lung disease. Thorax. 2019;74(10):965–76.

75.

Kooijmans

SAA

Stremersch

Braeckmans

de Smedt

Hendrix

Wood

MJA

Schiffelers

Raemdonck

Vader

. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release. 2013;172(1):229–38.

76.

Wang

Chen

Cheng

. Extracellular vesicles as an emerging drug delivery system for cancer treatment: current strategies and recent advances. Biomed Pharmacother. 2022;153:113480.

77.

Wang

Huang

Peng

Yao

Chen

Qiu

Wang

Chen

. Exosomes from M1-polarized macrophages enhance paclitaxel antitumor activity by activating macrophages-mediated inflammation. Theranostics. 2019;9(6):1714–27.

78.

Zheng

Zhu

Tang

Jiang

Huang

. Inhalable CAR-T cell-derived exosomes as paclitaxel carriers for treating lung cancer. J Transl Med. 2023;21(1):383.

79.

RuizdelRio

Guedes

Novillo

Lecue

Palanca

Cortajarena

Villar

. Fibroblast-derived extracellular vesicles as trackable efficient transporters of an experimental nanodrug with fibrotic heart and lung targeting. Theranostics. 2024;14(1):176–202.

80.

Pei

Zhang

Zhong

Yang

Zhang

. Exosome membrane-modified M2 macrophages targeted nanomedicine: treatment for allergic asthma. J Control Release. 2021;338:253–67.

81.

Wang

Zhou

Zhao

Peng

Wang

Zhang

Wan

, et al. Molecular targeting of intracellular bacteria by homotypic recognizing nanovesicles for infected pneumonia treatment. Biomater Res. 2025;29:0172.

82.

Pascucci

Coccè

Bonomi

Ami

Ceccarelli

Ciusani

Viganò

Locatelli

Sisto

Doglia

Parati

, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262–70.

83.

Zhang

Zhou

Ur-Rehman

Liang

Guo

Kong

, et al. In vivo self-assembled small RNAs as a new generation of RNAi therapeutics. Cell Res. 2021;31(6):631–48.

84.

Kannavou

Marazioti

Stathopoulos

Antimisiaris

. Engineered versus hybrid cellular vesicles as efficient drug delivery systems: a comparative study with brain targeted vesicles. Drug Deliv Transl Res. 2021;11(2):547–65.

85.

Haney

Klyachko

Zhao

Gupta

Plotnikova

Patel

Piroyan

Sokolsky

Kabanov

Batrakova

. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18–30.

86.

Shtam

Kovalev

Varfolomeeva

Makarov

Kil

Filatov

. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal. 2013;11:88.

87.

Liu

Yan

Popowski

Cheng

. Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity. Nat Nanotechnol. 2024;19(4):565–75.

88.

Popowski

Moatti

Scull

Silkstone

Lutz

López de Juan Abad

George

Belcher

Zhu

Mei

Cheng

, et al. Inhalable dry powder mRNA vaccines based on extracellular vesicles. Matter. 2022;5(9):2960–74.

89.

Bai

Duan

Liu

Luo

Cui

Xie

. Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells. Asian J Pharm Sci. 2019;15(4):461–71.

90.

Zhang

Wen

Liu

Sun

Chen

Cheng

Sun

Xiao

Wang

. S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells suppress ferroptosis and alleviate radiation-induced lung injury and long-term pulmonary fibrosis. J Nanobiotechnology. 2024;22(1):662.

91.

Popowski

López de Juan Abad

George

Silkstone

Belcher

Chung

Ghodsi

Lutz

Davenport

Flanagan

Piedrahita

, et al. Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung. Extracell Vesicle. 2022;1:100002.

92.

Liang

Duan

Xia

. Engineering exosomes for targeted drug delivery. Theranostics. 2021;11(7):3183–95.

Research advances of extracellular vesicles in lung diseases

Abstract

Keywords

Introduction

EVs from different sources

EVs derived from mesenchymal stem cells

EVs derived from immune cells

EVs from other sources

EVs isolation methods

Role of EVs in lung disease

EVs in lung disease diagnosis

EVs treatment of lung disease

Prospect

Footnotes

Acknowledgements

ORCID iD

Ethical Considerations

Statement of Human and Animal Rights

Statement of Informed Consent

Author Contributions

Funding

Declaration of Conflicting Interests

References