Role of Exosomes in Breast Cancer Management: Evidence-Based Review

Abstract

: The field of cancer research has massively grown in recent decades, leading to a better understanding of the underlying causes and greatly improved the therapeutic approaches. Breast cancer (BC) is the third leading cause of mortality among all cancers and the most common malignant disease in women worldwide, representing one in four cancers in women. The crosstalk between cancer cells and the surrounding microenvironment is crucial for tumor progression and metastatic process. Tumor cells communicate not only through classical paracrine signaling mechanisms, including cytokines, chemokines, growth factors, but also through“exosomes”. Exosomes are nano-vesicles that are released by various types of cells. Over the last decade, researchers have been attracted to the role of exosomes in breast cancer. It has been proven that exosomes influence major tumor-related pathways, including invasion, migration, epithelial-to-mesenchymal transition (EMT), metastasis, and drug resistance. Additionally, exosomes play important roles in clinical applications. Several studies have demonstrated the potential applications of exosomes in cancer therapy and diagnosis. Furthermore, exosomes have been engineered to function as nano-delivery systems of chemotherapeutic drugs. They can also be designed as vaccines to trigger the patient’s immune system. This review discusses the recent progress regarding the use of exosomes as drug delivery systems, therapeutic agents, biomarkers, and vaccines against breast cancer.

Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review

“…The new NPs, such as exosomes, human umbilical cord-derived mesenchymal stem cells (huc-MSCs), have been engineered to function as NDDSs of chemotherapeutic drugs against BC ( Cao et al, 2018 ; Al-Humaidi et al, 2021 ). Nano-formulations of medicinal plant extracts/essential oils and bioactive compounds will be of great importance for BC research ( Lahiani et al, 2017 ; Majidzadeh et al, 2020 ; Yap et al, 2021 ).…”

“…For optimal intracellular delivery, NPs should be able to evade degradation, have effective and efficient targeting ability, and facilitate the controlled release of drugs into the intracellular environment. To this end, multiple actively targeted NPs have been developed ( Prabaharan et al, 2009 ; Neves et al, 2013 ; Bilan et al, 2016 ; Park et al, 2017 ; Jin et al, 2018 ; Nowroozi et al, 2018 ; Patra et al, 2018 ; Sherje et al, 2018 ; Sun et al, 2018 ; Wang et al, 2018 ; Soltantabar et al, 2020 ; Al-Humaidi et al, 2021 ; Desai et al, 2021 ; Rommasi and Esfandiari, 2021 ; Giri et al, 2023 ). However, the cellular entry of nanocarriers is influenced by dynamic interactions between the carriers and the membrane.…”

“…NDDSs can exhibit a dramatic change in specific properties in response to characteristics of TME such as pH, temperature, light, reduction/oxidation, glutathione levels, and an abundance of certain enzymes ( Uthaman et al, 2018 ). To date, various NPs also have been used in the treatment of BC, including liposome NPs ( Nowroozi et al, 2018 ; Abumanhal-Masarweh et al, 2019 ; Le Rhun et al, 2020 ; Liu et al, 2022 ), SLNs ( Wang et al, 2018 ), PNPs ( Soltantabar et al, 2020 ), metal-based NPs (gold NPs) ( Jafarizad et al, 2017 ), SPIONs ( Poller et al, 2017 ), QDs ( Sun et al, 2018 )), carbon-based NPs ( Garriga et al, 2020 ), MSNs ( Zhao et al, 2018 ), protein-based NPs ( Esfandiari et al, 2016 ), dendrimers NPs ( Jain et al, 2019 ), and biological components such as exosomes ( Al-Humaidi et al, 2021 ). With respect to SDDS, nano-scale hybrid liposomes coated with magnetoliposomes have been used for intracellular magnetic targeting in BC ( Plassat et al, 2011 ).…”

Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

“…In the very last years, several reports have mainly focused on the idea that SEVs could be natural delivery vehicles to transport therapeutic drugs, antibodies, or RNAs to modify gene expression, especially in the cancer field [ 540 , 541 , 542 , 543 , 544 , 545 , 546 ] with a specific dedication to BC [ 547 , 548 , 549 , 550 ]. Indeed, SEVs are biocompatible, biodegradable, and, therefore, less toxic and immunogenic than other nanoparticle drug delivery systems such as liposomes or polymeric nanoparticles [ 551 ].…”

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

“…EV-mediated intracellular communication plays a role not only in maintaining cell homeostasis, but also in disease progression [ 96 , 97 , 98 , 99 ]. Exosomes are associated with several diseases, including cancer metastasis, which is the invasion and spread of primary cancer cells into other organs [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ]. Exosomes have been shown to play an important role in the formation of the cancer microenvironment and the mechanisms of cancer malignancy, such as cancer cell growth, infiltration, metastasis, and pre-metastasis niche [ 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 ].…”