Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Our plain-English summary of Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma, by S. Burgio, L. Noori, A. Marino Gammazza, et al (International Journal of Molecular Sciences, 2020).

The study

• Authors: S. Burgio, L. Noori, A. Marino Gammazza, C. Campanella, M. Logozzi, S. Fais, F. Bucchieri, F. Cappello, C. Caruso Bavisotto
• Journal: International Journal of Molecular Sciences
• Published: 2020;21(15)
• Type of article: Review
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

In plain English

This article was a review, not a new study. The authors surveyed cancer drug delivery approaches such as nanoparticles, liposomes and antibody-drug conjugates. They then focused on extracellular vesicles (EVs), tiny membrane sacs released by cells, as possible drug carriers. They applied this idea to malignant pleural mesothelioma (MPM), noting a latency of 15 to 60 years between asbestos exposure and disease onset. Because MPM is rare and preclinical MPM models are few and not reliable, much of the data reviewed came from other tumor types. Studies the authors cited reported that pleural effusions from patients were enriched in EVs secreted by the tumor, and that a protein analysis described a "mesothelioma exosomal signature" of 570 candidate proteins. The authors also cited work finding that none of the tissue or fluid markers tested was sensitive enough to tell benign from malignant pleural lesions. The authors proposed isolating EVs from cultured MPM cells and loading them with drugs after isolation. They noted that very little research on MPM-derived exosomes exists and that EVs lack clinical evaluation and standardized isolation methods.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of drug delivery strategies in cancer, focused on extracellular vesicles, with malignant pleural mesothelioma as the example
• Who was studied: No study population. The authors reviewed published literature on drug delivery systems and on extracellular vesicles in malignant pleural mesothelioma. Because MPM models are limited, they drew on data from other tumor types.
• Exposure: Not an exposure study. Asbestos is mentioned only as background, as the cause of MPM, with a stated latency of 15 to 60 years between exposure and disease onset.
• Main results:
  • The review reported that pleural effusion samples from patients, as described in cited studies, were enriched in EVs secreted by the tumor, particularly exosomes.
  • The review described a cited proteomic analysis of mesothelioma-derived exosomes. That analysis proposed a "mesothelioma exosomal signature" of 570 proteins as potential markers for early, minimally invasive diagnosis.
  • The review cited work by Bruno et al. finding that none of the tissue or soluble markers tested was sensitive enough to distinguish benign from malignant pleural lesions.
  • The review stated that BAP1 and p16 are not deleted in all MPMs, with sensitivity ranges reported in cited studies: 43% to 93% for p16 and 61 to 67% for BAP1.
  • The review reported, from cited literature, that MPM-derived exosomes mediate immune evasion by downregulating a receptor used by natural killer cells.
• The authors' conclusion: The authors proposed using EVs isolated from primary MPM cell cultures and modifying them with post-loading techniques to deliver drugs to the tumor.
• Limitations the authors state:
  • The authors stated that very little published work exists on the function of exosomes secreted by MPM.
  • The authors stated that preclinical MPM models are very few and not reliable, so data from other tumor types were used.
  • The authors listed among the disadvantages of EVs a lack of clinical evaluations.
  • The authors listed among the disadvantages of EVs a lack of standardized isolation methods.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma.

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• Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion — J. Javadi, A. Görgens, et al. (2021)
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