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Cited by 110Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryRNA Interference and Gene Delivery

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System

Open access
Li, Tianwei, Li, Xiaoqing, Han, Guiping, Liang, Ming, Yang, Zongrui, Zhang, Congyi, Huang, Shizhuan, Tai, Sheng +1 more·2022·Pharmaceutics
DOI 10.3390/pharmaceutics15010021PMC PMC9865231
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Abstract

Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30–100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.

AI snapshot

Written from the paper’s full text.

TL;DR

Exosomes are 30–100 nm endogenous extracellular vesicles that can serve as natural drug delivery carriers because of their biocompatibility, cargo-loading capacity, and engineerable targeting. This narrative review summarizes preclinical and clinical evidence for exosome-based delivery across cancer, neurological, autoimmune, skeletal, cardiovascular, urinary, cutaneous, and metabolic diseases, while emphasizing that clinical translation remains limited by manufacturing, standardization, and in vivo validation gaps.

Key findings

  • Exosomes are 30–100 nm biphospholipid vesicles rich in lipids, proteins, DNA, noncoding RNA, mRNA, and other active molecules; they can be loaded in vivo or in vitro and surface-modified by genetic and/or chemical engineering to improve targeting.
  • The review reports therapeutic applications in multiple disease areas, including cancer (e.g., Survivin-T34A with gemcitabine in pancreatic cancer, PTEN mRNA in glioma, miR-379 in breast cancer, PTX, cisplatin, doxorubicin, CRISPR/Cas9), neurological disease (e.g., siRNA delivery across the BBB, dopamine-loaded exosomes in Parkinson’s disease), autoimmune disease, skeletal disease, cardiovascular disease, urinary system disease, cutaneous disease, and metabolic disease.
  • In autoimmune disease, exosome-encapsulated methotrexate from MSCs showed better retention and a 10-fold inhibition of inflammation compared with methotrexate alone.
  • The first cancer diagnostic product based on exosome miRNA body fluid biopsy, ExoDx Lung (ALK), was launched in 2016 and could detect EML4-ALK mutations in non-small cell lung cancer patients in real time.

Methods

  • Narrative review focusing on the therapeutic potential and clinical significance of exosomes as carriers in drug delivery systems, with emphasis on homologous exosomes.
  • Evidence is drawn from cited preclinical and clinical studies and organized by disease category, including cancer, nervous, immune, skeletal, cardiovascular, urinary, cutaneous, and metabolic diseases.
  • Main synthesis is thematic, covering exosome formation, loading and modification strategies, advantages over synthetic carriers, and disease-specific applications; no systematic search strategy, inclusion criteria, or meta-analysis is described.

Limitations

  • The paper states that most research on exosome carriers remains in the in vitro stage; manufacture, purification, storage, stability duration, loading efficiency, and dosage still require optimization, and off-target effects are not fully prevented by surface modification.
  • The paper states that standardized testing for exosome-delivered drugs is lacking, few studies investigate the ultimate fate of exosomes, and isolation techniques such as NTA, DLS, and RPS cannot optimally separate exosomes from non-exosome contaminants; scalability, reproducibility, and regulatory translation also remain challenges.
  • Evident from the text: as a narrative review, it presents no primary experimental data, no systematic quality assessment, and relies on heterogeneous cited models and techniques, so the strength of individual therapeutic claims is not independently evaluated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/pharmaceutics15010021

Cites

133 of 133 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 120 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Exosomes are 30-100 nm in diameter.

    “As one of the endogenous extracellular vesicles, exosomes are 30–100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system.”
    • Also stated in: § 1. Introduction · boosted
      “Now, it is generally accepted that exosomes are 30–100 nm in diameter, rich in lipids (cholesterol, sphingomyelin, and ceramide), and fulfilled with active molecules including DNA, noncoding RNA, mRNA or protein (Table 1) [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Kowal, 2014, Biogenesis and secretion of exosomes, Curr. Opin. Cell Biol. source

      Not checked in the free run.

  • Premisenone given

    Remaining MVBs may merge with the membrane followed by secretion to the extracellular matrix to form new extracellular vesicles including exosomes.

    “The remaining MVBs may merge with the membrane followed by secretion to the extracellular matrix to form new extracellular vesicles including exosomes.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Artificial materials such as synthetic liposomes and polylactic acid have been exploited as carriers.

    “With the progress of science and technology, artificial materials such as synthetic liposomes and polylactic acid have been exploited as carriers in the last few years.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Higa, 2017, Ultra-small solid archaeolipid nanoparticles for active targeting to macrophages of the inflamed mucosa, Nanomedicine source

      Not checked in the free run.

    • cites [19] Lozano, 2018, Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment, Acta Biomater. source

      Not checked in the free run.

  • Premisenone given

    Exosomes from human donor cells can transfer chemical drugs or endogenous substances (proteins, mRNAs, miRNAs, lipids, etc.) to receiver cells for therapy.

    “During the exploiting their delivery function, exosomes from human donor cells are found to be capable of transferring chemical drugs or endogenous substances (proteins, mRNAs, miRNAs, lipids, etc.) to receiver cells for therapy.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Exosomes from human donor cells are capable of transferring chemical drugs or endogenous substances to receiver cells for therapy.
  • Premisecitation

    ESCRT is accepted as molecular media by which exosomes have specific cargo sorting functions.

    “The endosomal sorting complex required for transport (ESCRT) is accepted as molecular media by which exosomes have specific cargo sorting functions [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Li, 2022, Exosomes: Potential Biomarkers and Functions in Head and Neck Squamous Cell Carcinoma, Front. Mol. Biosci. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 14
  • May combine two claims. 57

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Exosomes widely participate in biological activities such as cell communication, migration, angiogenesis, immunomodulation, and proliferation.

    “Moreover, exosomes widely participate in biological activities such as cell communication, migration, angiogenesis, immunomodulation, and proliferation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Parts of MVBs can fuse to lysosomes, and their contents are degraded or recycled.

    “Parts of MVBs could be fused to lysosomes, and their contents are degraded or recycled.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Exosomes are regulated by cytokines, growth factors, proteins, distinct cell types, and other physicochemical conditions at multiple stages in production and widely exist in cells and body fluids in vivo, making them well-tolerated and -regulated.

    “In addition, exosomes are regulated by cytokines growth factors, proteins, distinct cell types, and other physicochemical conditions at multiple stages in the production process and widely exist in cells and body fluids in vivo, making them well-tolerated and -regulated [17].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Meldolesi, 2018, Exosomes and Ectosomes in Intercellular Communication, Curr. Biol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Unique tissue- or cell-specific proteins and genetic materials in exosomes help identify their cellular origin and the status of parental cells.

    “Those unique tissue- or cell-specific proteins and genetic materials help to identify their cellular origin and the status of parental cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Plant-derived exosomes have structures similar to mammalian exosomes and mediate plant-animal intercellular communication.

    “Even plant-derived exosomes have been characterized and shown to have structures similar to mammalian exosomes to mediate plant–animal intercellular communication [5].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Zhang, 2016, Plant derived edible nanoparticles as a new therapeutic approach against diseases, Tissue Barriers source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes are rich in lipids (cholesterol, sphingomyelin, and ceramide) and contain active molecules including DNA, noncoding RNA, mRNA, or protein.

    “Now, it is generally accepted that exosomes are 30–100 nm in diameter, rich in lipids (cholesterol, sphingomyelin, and ceramide), and fulfilled with active molecules including DNA, noncoding RNA, mRNA or protein (Table 1) [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Kowal, 2014, Biogenesis and secretion of exosomes, Curr. Opin. Cell Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ESCRT-0, ESCRT-I, and ESCRT-II may regulate cargo sorting, and ESCRT-III is involved in membrane endocytosis and exocytosis.

    “Studies have shown that ESCRT-0, ESCRT-I, and ESCRT-II may be regulating cargo sorting, and ESCRT-III is involved in membrane endocytosis and exocytosis.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [13] 2020, A Structural View on ESCRT-Mediated Abscission, Front. Cell Dev. Biol. source

      Not checked in the free run.

    • cites [14] Zhen, 2020, ESCRT-mediated phagophore sealing during mitophagy, Autophagy source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes can be released by tumor cells, immune cells, mesenchymal stem cells, and endothelial progenitor cells and are detectable in blood, cerebrospinal fluid, saliva, ascites, and urine.

    “Following in-depth investigations revealed that exosomes could be released by tumor cells, immune cells, mesenchymal stem cells, and endothelial progenitor cells and are widely detectable in blood, cerebrospinal fluid, saliva, ascites, and even urine [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Alikhani, 2011, Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages, J. Transl. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Exosomes are mainly formed by endocytosis of cell membranes, followed by converting to multivesicular bodies (MVBs).

    “Exosomes are mainly formed by endocytosis of cell membranes, followed by converting to multivesicular bodies (MVBs) with dynamic subcellular architecture.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Exosomes loaded with chemical or genetic drugs play a promising therapeutic role in diseases.

    “As an emerging drug delivery carrier, exosomes loaded with chemical or genetic drugs play a promising therapeutic role in diseases.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Exosomes are biphospholipid bodies formed from membranes and emitted by cells.

    “Exosomes are biphospholipid bodies formed from membranes and emitted by cells [1].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Boyiadzis, 2015, Information transfer by exosomes: A new frontier in hematologic malignancies, Blood Rev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Vps4 and ALIX participate in cargo sorting and exosome formation.

    “In addition, Vps4 and ALIX also participate in cargo sorting and exosome formation [15,16].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Jackson, 2017, Effects of Inhibiting VPS4 Support a General Role for ESCRTs in Extracellular Vesicle Biogenesis, Biophys. J. source

      Not checked in the free run.

    • cites [16] Larios, J., Mercier, V., Roux, A., and Gruenberg, J. (2020). ALIX- and ESCRT-III–dependent sorting of tetraspanins to exosomes. J. Cell Biol., 219. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Exosome biogenesis is controlled by related proteins including annexin and tetraspanins (CD63).

    “The biogenesis mechanism of exosomes is controlled by related proteins, including annexin and tetraspanins (CD63).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Exosomes as naturally derived biological carriers have been refined into the concept of drug delivery.

    “Therefore, exosomes as naturally derived biological carriers have been refined into the concept of drug delivery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Exosomes can be detected in almost any body fluids, indicating their transport cargo could go through membrane and be protected from degradations.

    “Exosomes could be detected in almost any body fluids (blood, cerebrospinal fluid, saliva, etc.), indicating their transport cargo could go through membrane and be protected from degradations [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Lai, 2013, Exosomes for drug delivery—A novel application for the mesenchymal stem cell, Biotechnol. Adv. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CMP-targeted CDC-derived exosomes increased cardiomyocyte uptake, decreased apoptosis, and promoted cardiac retention after intramyocardial injection.

    “After intramyocardial injection, they found that CMP-targeted CDC-derived exosomes could help in increasing cardiomyocyte uptake, decreasing apoptosis, and promoting cardiac retention.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Mentkowski, 2019, Exosomes Engineered to Express a Cardiomyocyte Binding Peptide Demonstrate Improved Cardiac Retention in Vivo, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Artificial carrier materials have disadvantages including low transduction efficiency, lack of target specificity, rapid degradation, and toxicity.

    “However, these materials have the following disadvantages: low transduction efficiency, lack of target specificity, rapid degradation, and toxicity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Exosomes contain a plentiful number of proteins and genetic molecules, allowing most biological substances to be loaded without unexpected interactions with the carrier.

    “A plentiful number of proteins and genetic molecules as a component in exosomes indicate that the great majority of biological substances can be loaded without unexpected interactions with the carrier.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Wei, 2021, Regulation of exosome production and cargo sorting, Int. J. Biol. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes have superior compatibility critical to their function as carriers and a tremendous inherent capacity for receiver cells.

    “They have superior compatibility that is critical to their function as carriers [28], which also shows a tremendous inherent capacity for receiver cells [29].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [28] Wei, 2021, Regulation of exosome production and cargo sorting, Int. J. Biol. Sci. source

      Not checked in the free run.

    • cites [29] Anand, 2019, Ticket to a bubble ride: Cargo sorting into exosomes and extracellular vesicles, Biochim. Biophys. Acta Proteins Proteom. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AA-modified PTX-loaded exosomes had better loading capacity and therapeutic efficiency in vivo.

    “Their result showed that AA-modified vesicles had a better loading capacity and therapeutic efficiency in vivo [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Kim, 2018, Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: In vitro and in vivo evaluations, Nanomedicine source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Protein corona causes an immune response and is quickly cleared from the blood.

    “Furthermore, the protein corona causes an immune response and is quickly cleared from the blood (Figure 2) [36,37].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] Xiao, 2021, The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood-brain barrier and attenuates their targeting ability to brain tumor, Biomaterials source

      Not checked in the free run.

    • cites [37] Sutaria, 2017, Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading, Pharm. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes can cross the blood-brain barrier and transport specific drugs to neural cells, significantly retaining side effects including toxicity.

    “For instance, exosomes can cross the blood–brain barrier (BBB) and transport specific drugs to the neural cell [39], significantly retaining side effects including toxicity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Zhang, 2015, Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury, J. Neurosurg. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unlike synthetic liposomes, exosomes can be loaded with cargo in vivo by transfection and in vitro by electroporation and lipofection.

    “Unlike synthetic liposomes, exosomes can be loaded with cargo in vivo by transfection and in vitro by electroporation and lipofection [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Xi, 2021, Drug loading techniques for exosome-based drug delivery systems, J. Pharm. Sci.

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Exosomes are capable to refrain from phagocytosis and cross biological barriers with therapeutic substances to sites that are difficult to arrive at by artificial carriers.

    “With the above advantages, exosomes are capable to refrain from phagocytosis and cross biological barriers with therapeutic substances (proteins, mRNAs, lipids, chemical drugs) to sites that are difficult to arrive at by artificial carriers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Exosomes have good biocompatibility as carriers, which can prolong the circulation half-time with therapeutic cargo.

    “Therefore, exosomes have good biocompatibility as carriers, which can prolong the circulation half-time with therapeutic cargo [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Fernandes, 2020, Exosome-like Nanoparticles: A New Type of Nanocarrier, Curr. Med. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DC-derived exosomes gain MHC-I that combines with tumor-derived peptides, and the complex could activate NK or T cells to suppress tumors.

    “Notably, DC-derived exosomes gain MHC-I that combines with tumor-derived peptides, and the complex could activate NK or T cells to suppress tumors [45,46].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [45] Hartman, 2011, Increasing vaccine potency through exosome antigen targeting, Vaccine source

      Not checked in the free run.

    • cites [46] Romagnoli, 2015, Dendritic Cell-Derived Exosomes may be a Tool for Cancer Immunotherapy by Converting Tumor Cells into Immunogenic Targets., Front. Immunol. source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Exosomes show good biocompatibility, non-immunogenicity, and biodegradability and are intensively investigated in the therapeutic role for different diseases.

    “With the promising and highly efficient carry potentials in DDS, exosomes are showing good biocompatibility, non-immunogenicity, and biodegradability and intensively investigated in the therapeutic role for different diseases.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Strong immunogenic proteins embedded in exosomes may provoke immune activation to inhibit cancer proliferation with the potential for developing cancer vaccines.

    “Furthermore, strong immunogenic proteins embedded in exosomes may provoke immune activation to inhibit cancer proliferation with the potential for developing cancer vaccines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Exosomes rich in genetic material, proteins, and lipids may carry effective communication information for donor and target cells, which may build up the tumor microenvironment.

    “Exosomes rich in genetic material, proteins, and lipids may carry effective communication information for donor cells and target cells, which may build up the tumor microenvironment (TME) [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Li, 2019, Exosomes in the tumor microenvironment as mediators of cancer therapy resistance, Mol. Cancer source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Exosome transport solves the problem of easy degradation of miRNAs in vivo, implying a new tumor therapy.

    “Furthermore, exosome transport solves the problem of easy degradation of miRNAs in vivo, implying a new tumor therapy [50].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Ell, 2013, Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis, Cancer Cell source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    TDEs could be devised as natural drug carriers with higher cancer cell targeting and therapeutic efficacy, low toxicity, and permeability.

    “Therefore, TDEs could be devised as natural drug carriers with higher cancer cell targeting and therapeutic efficacy, low toxicity, and permeability [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Tarasov, 2021, Extracellular vesicles in cancer nanomedicine. Semin, Cancer Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In pancreatic cancer, exosomes loaded with T34A protein induced apoptosis and enhanced the gemcitabine-killing effect.

    “In pancreatic cancer, it was shown that exosomes loaded with the survival protein-T34A protein induced apoptosis and enhanced the gemcitabine-killing effect [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Aspe, 2014, Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant, J. Extracell. Vesicles source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes pre-loaded with cisplatin significantly decrease liver or kidney toxicities and suppress tumors in ovarian cancer mice xenograft model.

    “Tang et al. showed another example that exosomes pre-loaded with cisplatin could significantly decrease liver or kidney toxicities and suppress tumors in ovarian cancer mice xenograft model [58].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Tang, 2012, Delivery of chemotherapeutic drugs in tumour cell-derived microparticles, Nat. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tumor cell-derived exosomes can be a useful vehicle for paclitaxel from the parental cell, carrying the drug into recipient cells through endocytosis and increasing cytotoxicity.

    “For example, Saari et al. showed that tumor cell-derived exosomes could be considered a useful vehicle for paclitaxel from the parental cell, carrying the drug into recipient cells through the endocytosis pathway and increasing their cytotoxicity [56].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [56] Saari, 2015, Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells, J. Control. Release source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Antitumor drugs such as vincristine, curcumin, PTX, and camptothecin generally have poor stability, low solubility, high hydrophobicity, and short half-life, limiting clinical application.

    “Antitumor drugs such as vincristine, curcumin, PTX, camptothecin, etc., most of which are monomer active ingredients extracted from Chinese medicine, generally have disadvantages including poor stability, low solubility, high hydrophobicity, and short half-life, etc. Therefore, their low bioavailability limited the clinical application.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The PSiNP system exhibits remarkable cell absorption and cytotoxicity in tumor cells.

    “In addition, this system exhibits remarkable cell absorption and cytotoxicity in tumor cells [61].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [61] Yong, 2019, Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy, Nat. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MSC-derived exosomes containing miR-379 have a therapeutic effect on breast cancer, with significantly reduced tumor growth rates in T47D breast cell line expressing miR-379.

    “Brien et al. reported that mesenchymal stem cells (MSC)-derived exosomes containing miR-379 were shown to have a therapeutic effect on breast cancer, with significantly reduced tumor growth rates in T47D breast cell line expressing miR-379 [51].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Khan, 2018, Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379, Oncogene source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Exosome carriers possess superior biocompatibility, causing drugs more easily uptake by the cells and avoiding drug resistance.

    “Therefore, exosome carriers possess superior biocompatibility, causing drugs more easily uptake by the cells and avoiding drug resistance (Figure 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Nefmut loaded into exosomes and fused with a single-chain fragment variable antibody at its C-terminus forms engineered exosomes, proposing a novel targeted strategy for neurodegenerative diseases.

    “The researchers loaded Nefmut into exosomes and fused a single-chain fragment variable antibody at its C-terminus to form engineered exosomes, which proposed a novel targeted strategy for endogenous engineering in the treatment of neurodegenerative diseases based on exosomes released by the cellular composition of the CNS [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Ferrantelli, F., Chiozzini, C., Leone, P., Manfredi, F., and Federico, M. (2020). Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases. Pharmaceutics, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Engineered DC-derived exosomes with Lamp2b and RVG peptide loaded with exogenous siRNA specifically delivered cargo to neurons in the brain, downregulating the siRNA target gene and impacting Alzheimer's disease.

    “Notably, exosomes specifically delivered loaded cargo to neurons in the brain, downregulating the siRNA target gene and impacted on Alzheimer’s disease (AD) [70].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] Seow, 2011, Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes, Nat. Biotechnol. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In the central nervous system, exosomes have a role in mediating intercellular communication, maintaining homeostasis, and neuroprotective.

    “In the central nervous system (CNS), exosomes have a role in mediating intercellular communication, maintaining homeostasis, and neuroprotective (Table 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    TDEs contain tumor-associated antigens that can preferably identify tumors and targeted transmit therapeutic substances.

    “In summary, TDEs contain tumor-associated antigens that can preferably identify tumors and targeted transmit therapeutic substances.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Tumor-derived exosomes contain tumor-associated antigens that can preferably identify tumors.

  • May combine two claims.

    Premisecitation

    Engineered exosome strongly improved treatment of glioma while reducing side effects.

    “Their findings demonstrated that the engineered exosome strongly improved the treatment of glioma while reducing side effects [62].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [62] Jia, 2018, NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo, Biomaterials source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Encapsulating methotrexate in MSC exosomes showed better retention and a 10-fold inhibition of inflammation compared to methotrexate alone.

    “To suppress the side effects of methotrexate, researchers encapsulated the chemical drug in exosomes from MSCs, and it showed better retention and a 10-fold inhibition of inflammation compared to methotrexate alone [80].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Neupane, 2020, Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune Diseases, Curr. Pharm. Des. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Glutathione-loaded exosomes were more able to shorten the glutathione synthesis process, increase glutathione serum levels, and reduce rheumatoid factors.

    “Similarly, Kadry et al. found the glutathione-loaded exosomes were more able to shorten the glutathione synthesis process, increase glutathione serum levels, and meanwhile reduce rheumatoid factors.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Kadry, 2019, Liposomal glutathione as a promising candidate for immunological rheumatoid arthritis therapy, Heliyon source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Engineered exosomes loaded with IL-4 decreased experimental autoimmune encephalomyelitis score sharply and significantly reduced tissue damage.

    “After applying the above exosomes, the experimental autoimmune encephalomyelitis score decreased sharply, significantly reducing tissue damage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Casella, 2018, Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis, Mol. Ther. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Engineered exosomes modified with folic acid, PEG, and cholesterol loaded with dexamethasone sodium phosphate better protected bone and cartilage in CIA mice and reduced joint inflammation without obvious liver toxicity.

    “In vivo biodistribution experiments showed that these engineered exosomes better protected bone and cartilage in CIA mice and reduced joint inflammation without obvious liver toxicity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [82] Yan, 2020, Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis, J. Nanobiotechnol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Conjugating STExo surface with BMSC-specific aptamers significantly increased efficiency, confirming the novel modification could help in osteoporosis and fractures.

    “The researchers found significantly higher efficiency after conjugating the STExo surface with BMSC-specific aptamers, confirming the novel modification could help in osteoporosis and fractures [87].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [87] Luo, 2019, Aptamer-functionalized exosomes from bone marrow stromal cells target bone to promote bone regeneration, Nanoscale source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Injecting miR-19a-3p-loaded exosomes into mouse myocardium resulted in improved angiogenesis, decreased myocardial fibrosis, and increased left ventricular ejection fraction.

    “For example, injecting miR-19a-3p-loaded exosomes into mouse myocardium revealed that exosomes resulted in improved angiogenesis, decreased myocardial fibrosis, and increased left ventricular ejection fraction [92].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Graber, 2010, miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy, Cardiovasc. Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Targeting KGN to SF-MSCs by engineered exosomes resulted in uniform dispersion of KGN in the cytoplasmic matrix, increased concentration in the target, and significantly promoted chondrogenesis of SF-MSCs.

    “Another study showed that targeting Kartogenin (KGN) to synovial fluid-derived mesenchymal stem cells (SF-MSCs) by engineered exosomes resulted in uniform dispersion of KGN in the cytoplasmic matrix, increased concentration in the target, and significantly promoted chondrogenesis of SF-MSCs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Xu, 2021, Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration, Biomaterials source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Treatment of engineered bone scaffolds with exosomes as carriers provides direct bracing for bone defects and a suitable status for bone regeneration.

    “Moreover, the treatment of the engineered bone scaffolds with exosomes as carriers not only provides direct bracing for bone defects but also provides a suitable status for bone regeneration.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Adipose tissue-derived stem cell exosomes can accelerate collagen synthesis and redeposition through regulating PI3K/Akt pathway, reducing healing time and scarring in mouse models.

    “Similarly, Zhang et al. found that exosomes from adipose tissue-derived stem cells can accelerate collagen synthesis and redeposition through regulating PI3K/Akt pathway. This function helps in full-thickness skin wounds, ultimately reducing healing time and scarring in mouse models [103].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Zhang, 2018, Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway, Exp. Cell Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HUVEC-derived exosomes can promote collagen maturation and angiogenesis and regulate keratinocytes and fibroblast growth, thereby accelerating skin wound healing.

    “For example, exosomes derived from human umbilical vein endothelial cells (HUVECs) can promote collagen maturation and angiogenesis and regulate the keratinocytes and fibroblast growth, thereby accelerating skin wound healing [102].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Zhao, 2020, GelMA combined with sustained release of HUVECs derived exosomes for promoting cutaneous wound healing and facilitating skin regeneration, Histochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    M1-Exo-GEM had significantly up-regulated expression of inflammatory cytokines and stronger cytotoxic effect on cancer cells compared with M1-Exo and GEM.

    “Compared with M1-Exo and GEM, M1-Exo-GEM had significantly up-regulated the expression of inflammatory cytokines and stronger cytotoxic effect on cancer cells [100].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] Tang, 2022, M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine, Aging source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mel@NVs could promote formation of microvessels and alleviate cardiac fibrosis, thereby restoring mitochondrial dysfunction for myocardial repair.

    “Further reports showed the Mel@NVs could promote the formation of microvessels and alleviate cardiac fibrosis, thereby further restoring mitochondrial dysfunction for myocardial repair.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] Zhang, 2022, Melatonin Engineered Adipose-Derived Biomimetic Nanovesicles Regulate Mitochondrial Functions and Promote Myocardial Repair in Myocardial Infarction, Front. Cardiovasc. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Exosomes can deliver chemical drugs, nucleic acids, and proteins.

    “enable exosomes to deliver substances such as chemical drugs, nucleic acids, and proteins, etc.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Exosomes have a higher safety profile that escapes from immune detection systems.

    “a higher safety profile that escapes from immune detection systems”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Exosome microRNAs from hypoxic BMSCs were selectively taken up by lung cancer cells and could activate STAT3 signaling to induce epithelial-mesenchymal transition to promote invasion of lung cancer cells.

    “Similarly, Zhang et al. showed that exosome microRNAs (such as miR-193a-3p, miR-210-3p, and miR-5100) from hypoxic BMSCs were selectively taken up by lung cancer cells and could activate STAT3 signaling to induce epithelial–mesenchymal transition (EMT) to promote the invasion of lung cancer cells, which has been identified as a new biomarker for lung cancer progression [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Zhang, 2019, Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT, Mol. Cancer source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosome-based miR-125b may accelerate myofibroblast differentiation and transfer to young fibroblast by targeting SIRT7, promising for counteracting skin aging.

    “Xia et al. found that exosome-based miR-125b may accelerate myofibroblast differentiation and transfer to young fibroblast by targeting SIRT7. The results show a promising method for counteracting skin aging [107].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Xia, 2022, Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing, J. Nanobiotechnol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Exosomes have a better-tolerated and longer-circulating half-life, which prolongs the cargo from degradation.

    “a better-tolerated and longer-circulating half-life, which prolongs the cargo from degradation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Exosomes have easy targeting ability, as their surface can be artificially modified to increase biological effects as carriers and targeted transport.

    “a more easy targeting ability, by which the exosomes’ surface could be artificially modified to increase biological effects as carriers and targeted transport”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    VH-EV promoted function of HUVECs in vitro through HIF-1α signaling and displayed great therapeutic effects on skin regeneration.

    “Similarly, Wang et al. loaded epidermal stem cell (ESC)-derived exosomes with VH298 (VH-EV), and VH-EV was shown to promote the function of HUVECs in vitro through HIF-1α signaling. This special exosome displayed great therapeutic effects on skin regeneration [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Wang, 2022, VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis, Acta Biomater. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Exosomes secreted by cells in different tissues carry different biological components.

    “Exosomes secreted by cells in different tissues carry different biological components”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Exosomes are involved in the occurrence and progression of various systemic diseases.

    “exosomes are involved in the occurrence and progression of various systemic diseases”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Exosomes have intrinsic properties of high biocompatibility and low immunogenicity.

    “which determine their intrinsic properties of high biocompatibility and low immunogenicity”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Methods to regulate cargo packaging and vesicle release in vivo are still limited.

    “methods to regulate cargo packaging and vesicle release in vivo are still limited”
    Quote in the paperNot a substantial claim
66 of 66

  • The paper relies on this without support.

    Current studies on heterologous exosomes lack clinical application because of possible immune responses and lack of targeting.

    “Due to the possible immune responses and lack of targeting, current studies on heterologous exosomes lack their clinical application, we mainly reviewed the role of homologous exosomes as drug delivery carriers.”

  • The paper relies on this without support.

    Exosomes from human donor cells are capable of transferring chemical drugs or endogenous substances to receiver cells for therapy.

    “During the exploiting their delivery function, exosomes from human donor cells are found to be capable of transferring chemical drugs or endogenous substances (proteins, mRNAs, miRNAs, lipids, etc.) to receiver cells for therapy.”

  • The paper relies on this without support.

    Therapeutic miRNAs neither penetrate the skin nor easily cross cell membranes.

    “In addition, as carriers, exosomes provide an emerging delivery method for therapeutic miRNAs that neither penetrate the skin nor easily cross cell membranes.”

  • The paper relies on this without support.

    Tumor-derived exosomes contain tumor-associated antigens that can preferably identify tumors.

    “In summary, TDEs contain tumor-associated antigens that can preferably identify tumors and targeted transmit therapeutic substances.”

  • The paper relies on this without support.

    Most research on exosome carriers is still in the in vitro stage.

    “most of the research on exosome carriers is still in the vitro stage”

  • The paper relies on this without support.

    Existing results enhanced the interaction of exosomes with their targets by modifying exosome surface proteins, but did not counteract the natural homing ability of exosomes, nor prevent off-target effects.

    “existing results enhanced the interaction of exosomes with their targets by modifying exosome surface proteins, but they did not counteract the natural homing ability of exosomes, nor did they prevent off-target effects”

  • The paper relies on this without support.

    There is currently a lack of standardized testing for drugs delivered by exosomes.

    “There is currently a lack of standardized testing for drugs delivered by exosomes”

  • The paper relies on this without support.

    There are few studies investigating the ultimate fate of exosomes.

    “few studies investigating the ultimate fate of exosomes”

  • The paper relies on this without support.

    Most previous studies on exosome therapy only involve in vitro models.

    “most of them only involve in vitro models”

  • The paper relies on this without support.

    It is unclear whether previous in vitro results reflect in vivo processes.

    “it is unclear whether these results reflect in vivo processes”

  • The paper relies on this without support.

    Most previous studies simply analyzed a certain number of miRNAs or proteins.

    “most of these studies simply analyzed a certain number of miRNAs or proteins”

  • The paper relies on this without support.

    There is a lack of understanding of exosomes with abundant biological information from distinct cell types.

    “There is a lack of understanding of the exosomes with abundant biological information from distinct cell types”

  • The paper relies on this without support.

    The physical characteristics of exosomes (size, shape, surface charge, density) are necessary to determine their role and function.

    “The physical characteristics of the exosome (including size, shape, surface charge, and density) are necessary to determine its role and function”

  • The paper relies on this without support.

    Challenges remain in reliably tracking exosomes in vivo.

    “challenges remain in reliably tracking exosomes in vivo”

  • The paper relies on this without support.

    The scalability or reproducibility of exosome production is a challenge.

    “the scalability or reproducibility of exosome production is also one of the challenges”

  • The paper relies on this without support.

    Translations of exosomes into clinics are confined within existing regulatory frameworks.

    “the translations of exosomes into clinics are confined within existing regulatory frameworks”
16 of 16

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Preclinical studies have demonstrated the benefits of exosome-based mRNA therapies, which are moving toward clinical trials.

    “Preclinical studies have demonstrated the benefits of exosome-based mRNA therapies, which are moving toward clinical trials [88].”

    From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [88]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • TBI treatment claim cites an osteosarcoma study

    Minor

    The text attributes a TBI apoptosis result to Wang et al. [72], but reference 72 is titled as a study of doxorubicin-loaded exosomes for osteosarcoma treatment in vitro.

  • Glucocorticoid-loaded exosomes claim cites nano-liposomes

    Minor

    The claimed treatment uses exosomes, whereas the cited reference identifies the glucocorticoid carriers as nano-liposomes.

  • Glutathione-loaded exosomes claim cites liposomal glutathione

    Minor

    The text describes glutathione-loaded exosomes, but the cited study's title describes liposomal glutathione instead.

3 of 3

Cites

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Cited by

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Related

Authors
Li, T., Li, X., Han, G., Liang, M., Yang, Z., Zhang, C., Huang, S., Tai, S., & Yu, S.
Affiliations
  • Harbin Medical University (CN)
  • Second Affiliated Hospital of Harbin Medical University (CN)
Corresponding author
  • Tai, Sheng
  • Yu, Shan
ORCID
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2022-12-21
Volume
15
Issue
1
Pages
21
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics15010021
PMC
PMC9865231
OpenAlex
W4313469795
Semantic Scholar
287afb9769707e5e6570f2e2c823a26dcb28688a
Cited by
110
References
131
Citations by year
2026: 28 · 2025: 36 · 2024: 36 · 2023: 10
FWCI
2.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Natural Science Foundation of China (81972724)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
exosomes, drug delivery systems, extracellular vesicles, targeted drug delivery, exosome surface modification, cargo loading, intercellular communication, cancer therapy, neurological disorders, immune disorders, bone disease

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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