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sHarnessing Exosomes and Bioinspired Exosome-Like Nanoparticles for siRNA Delivery
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Mei Lu, Haonan Xing, Yuanyu Huang
Extracellular vesicles (EVs) are heterogeneous membrane-enclosed vesicles that are secreted by (almost) all cell types and play important roles in intercellular communication. Defined by size and sub-cellular origin, EVs are generally classified into three subtypes, including exosomes, microvesicles, and apoptotic bodies (Lu, Xing, Xun et al. 2018a; Raposo and Stoorvogel 2013). Among these vesicles, current research interest primarily focuses on exosomes and microvesicles, as the large size of apoptotic bodies (50–5000 nm) rules out their potential for therapeutic application. Exosomes with size ranging from 50 to 150 nm are the smallest vesicles originated from intraluminal budding of multivesicular bodies (MVBs), while microvesicles (50–1000 nm) are secreted by directly budding and fission of the plasma membrane. Despite the apparent differences, it still remains difficult to distinguish different subsets of EVs for current isolation techniques (Piffoux et al. 2019; Kowal et al. 2016). Therefore, in this chapter, we used the term exosomes that is mainly referred to exosomes and microvesicles.
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Thomas J. Anchordoquy, Yechezkel Barenholz, Diana Boraschi, Michael Chorny, Paolo Decuzzi, Marina A. Dobrovolskaia, Z. Shadi Farhangrazi, Dorothy Farrell, Alberto Gabizon, Hamidreza Ghandehari, Biana Godin, Ninh M. La-Beck, Julia Ljubimova, S. Moein Moghimi, Len Pagliaro, Ji-Ho Park, Dan Peer, Erkki Ruoslahti, Natalie J. Serkova, Dmitri Simberg
It was pointed out that, unlike intravascular targets, extravascular/tumor receptors are not easily accessible to nanomedicines, and the concentration of these target receptors is typically in the picomolar range. Thus, strategies should be developed to open the tumor endothelial barrier. Several other novel approaches were presented that could enhance tumor penetration. Changing the tumor microenvironment by radio frequency (RF) or by high-intensity focused ultrasound (HIFU) can effectively remodel the tumor microenvironment while concomitantly enhancing nanodrug accumulation, thereby leading to significantly improved therapeutic efficacy [16]. However, these methods are obviously insufficient when treatment of disseminated disease is contemplated. Extracellular vesicles, a natural transport system, can be hijacked to mediate intercellular migration of exogenous hydrophobic compounds through multiple cell layers, both in vitro and in vivo. This approach would significantly improve the therapeutic efficacy of hydrophobic compounds in poorly vascularized tumors [17]. Another strategy presented was to use the natural tropism of cell-derived vesicles to tumors. Thus, ghosts of stem cells (nanoghosts) associate with tumor cells through cellular uptake (endocytosis pathways) and via cellular binding (adsorption, lipid exchange, fusion). These interactions enable targeting of anticancer therapeutics to different compartments of the cancer cell, significantly enhancing delivery of payloads to tumors [18].
Exosomes in Cancer Disease, Progression, and Drug Resistance
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Taraka Sai Pavan Grandhi, Rajeshwar Nitiyanandan, Kaushal Rege
Exosomes are cell-type-dependent extracellular vesicles, 30–150 nm in dimension, that play a critical role as mediators of communication between different cell types in the body [1]. Exosomes consist of a lipid bilayer enclosing cargo of DNA, RNA and/or proteins and are directed to a specific destination [2–6] by means of proteins displayed on their surface [7]. These extracellular vesicles are produced by all cells of the body [8–10] and were previously considered as cellular waste or debris without a significant biological role. However, recent studies have shed light on the diverse roles exosomes and their contents play in multiple disease biologies [11]. Exosomal delivery of cargo for communication is now considered a key means of cell-cell communication in addition to that mediated by cell-cell contact and soluble molecules [12]. Unsurprisingly, these messengers play an important role in the growth and metastasis of cancer cells [13–16], including in actively preparing distant metastatic sites for organotropic cancer progression [7, 15, 17]. Exosomes have also been demonstrated to play a role in active modulation of the microenvironment [18–21]. These roles have led to the emergence of exosomes as promising biomarkers for cancer disease progression, metastases, and recurrence [22–27]. In this chapter, we review the roles of exosomes in cancer growth and progression (metastases) and their promise as biomarkers and immunotherapeutics in cancer. Details on the methods of isolation and purification of exosomes and use of exosomes as nanocarriers of nucleic acids for cancer therapy are described in our previous review [28].
Expression levels of selected cytokines and microRNAs in response to vitamin D supplementation in ultra-marathon runners
Published in European Journal of Sport Science, 2020
D. Pastuszak-Lewandoska, D. Domańska-Senderowska, J. Kiszałkiewicz, P. Szmigielska, A. Snochowska, W. Ratkowski, M. Spieszny, T. Klocek, P. Godlewski, P. Cięszczyk, E. Brzeziańska-Lasota, A. V. September, M. J. Laguette
The design of this study, linking the expression levels of mRNAs of several pro-inflammatory factors to inflammatory miRNAs together with the influence of vitamin D supplementation, does not replicate any early work performed in ultra-marathon runners. However, further larger studies are required towards the recognition of the studied cytokines and miRNAs as direct markers of overtraining and adaptation to extreme exercise dose. The origin of the circulating exosomal inflamma-miRs also warrants further investigation. These structures are extracellular vesicles generated by all cell types and play key roles in intercellular communication. It is plausible that they originate from the muscles after the extreme endurance exercise (UM) or immune cells as a result of the strenuous physical activity.
Latest advances in extracellular vesicles: from bench to bedside
Published in Science and Technology of Advanced Materials, 2019
Tomofumi Yamamoto, Nobuyoshi Kosaka, Takahiro Ochiya
It has been shown that almost all of the cells release various types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. EVs vary in size, properties, and secretion pathway depending on the originated cells, and the EVs are indeed taken up by recipient cells via a variety of mechanisms (Figure 1) [1,2]. Exosomes are small EVs (sEVs), their diameter is approximately 100 nm. Exosomes are initially formed by a process of inward budding in early endosomes to form multivesicular bodies (MVBs) and released into the extracellular microenvironment to transfer their components [3,4]. Microvesicles (MVs) are larger than exosomes, approximately 100–1000 nm, and are composed of lipid components of plasma membrane [5]. MVs are synthesized in directly shedding or budding from plasma membranes. Apoptotic bodies have various sizes (1–5 μm), and only when cells are killed by the process of programmed cell death, resulting in secretion of apoptotic bodies. These various types of EVs have similar characteristics, such as size and density. Thus, more detailed classification is required for EV research. Although the role of EVs was initially supposed to be cellular waste management, such as, throwing unwanted proteins and biomolecules [6], in 2007, Valadi et al. have shown that EVs have contained mRNA in their lumen as well as microRNAs (miRNAs), which is considered a novel cell to cell communication tools [7]. In a few years from that year, several groups demonstrated that EVs transferred their functional miRNAs to recipient cells [8–11].
Indocyanine green-loaded exosomes for image-guided glioma nano-therapy
Published in Journal of Experimental Nanoscience, 2022
Bo Fan, Song Yang, Yuan-yu Wang, Chao Zhang, Ji-peng Yang, Li-qun Wang, Zhong-qiang Lv, Xue-fang Shi, Zhen-zeng Fan, Jian-kai Yang
Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells. Exosomes were found in biological fluids, including blood, urine and cerebrospinal fluid, as well as tissue matrix (matrix-bound nanovesicles) [2]. Exosomes that contain variety of molecular constituments of their original cells, including protein, DNA and various RNAs, can be released from cells, and their component profiles vary based on the cell and tissue of origin. Therefore, exosomes are identified as key players in cancer and potential therapeutic strategy [3].