Exosomes: the ideal nanovectors for biodelivery

2013 ◽  
Vol 394 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Stefano Fais ◽  
Mariantonia Logozzi ◽  
Luana Lugini ◽  
Cristina Federici ◽  
Tommaso Azzarito ◽  
...  

Abstract Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tom O. J. Cockram ◽  
Jacob M. Dundee ◽  
Alma S. Popescu ◽  
Guy C. Brown

Mammalian phagocytes can phagocytose (i.e. eat) other mammalian cells in the body if they display certain signals, and this phagocytosis plays fundamental roles in development, cell turnover, tissue homeostasis and disease prevention. To phagocytose the correct cells, phagocytes must discriminate which cells to eat using a ‘phagocytic code’ - a set of over 50 known phagocytic signals determining whether a cell is eaten or not - comprising find-me signals, eat-me signals, don’t-eat-me signals and opsonins. Most opsonins require binding to eat-me signals – for example, the opsonins galectin-3, calreticulin and C1q bind asialoglycan eat-me signals on target cells - to induce phagocytosis. Some proteins act as ‘self-opsonins’, while others are ‘negative opsonins’ or ‘phagocyte suppressants’, inhibiting phagocytosis. We review known phagocytic signals here, both established and novel, and how they integrate to regulate phagocytosis of several mammalian targets - including excess cells in development, senescent and aged cells, infected cells, cancer cells, dead or dying cells, cell debris and neuronal synapses. Understanding the phagocytic code, and how it goes wrong, may enable novel therapies for multiple pathologies with too much or too little phagocytosis, such as: infectious disease, cancer, neurodegeneration, psychiatric disease, cardiovascular disease, ageing and auto-immune disease.


2020 ◽  
Vol 245 (10) ◽  
pp. 845-850 ◽  
Author(s):  
Heon-Jin Lee

Extracellular RNAs (exRNAs) are released by extracellular vesicles, small membranous nanoparticles secreted by all cell types. When transported into cells, exRNAs can modulate gene expression or cellular responses in the target cells since many small RNAs have regulatory functions. Indeed, it is widely acknowledged that endogenous exRNAs in the human body are related to various diseases. However, microbial exRNAs have been less studied, and their connection to host diseases has just begun to be explored. In this review, I will discuss analytical methods for exRNAs and the potential use of exRNAs as disease biomarkers. I also consider current progress in understanding the regulation of host mechanisms by microbial exRNAs as inter-kingdom communication, efforts to utilize extracellular vesicles as therapeutic vehicles loaded with engineered RNA cargos, and a putative connection between microbial exRNA-based regulation of host responses and human diseases such as Alzheimer’s. This overview aims to present novel insights into pathogenesis with regard to the function of microbial exRNAs as “disease-relevant travelers.” Impact statement The number of commensal bacteria in the body surpasses the number of actual human cells. Thus, various interactions between microbes and human cells constitute an inevitable phenomenon. Recent evidence has led to bacterial extracellular RNAs (exRNAs) being proposed as good candidates for microbe–host inter-kingdom communication tools as they can modulate the expression of host genes. However, research findings on the relevance of interactions between extracellular RNA and human diseases are still in their infancy. Nevertheless, substantial data suggest that microbial exRNAs are implicated in various human diseases both at local and distant sites. By exploring various scenarios for the involvement of microbial exRNAs in human diseases, we may better understand the role of exRNAs as “communication signals” for diseases and thereby develop novel therapeutic strategies by using them and their carrier extracellular vesicles.


Mathematics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 157 ◽  
Author(s):  
A. Elaiw ◽  
E. Elnahary

This paper deals with the study of an HIV dynamics model with two target cells, macrophages and CD4 + T cells and three categories of infected cells, short-lived, long-lived and latent in order to get better insights into HIV infection within the body. The model incorporates therapeutic modalities such as reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). The model is incorporated with distributed time delays to characterize the time between an HIV contact of an uninfected target cell and the creation of mature HIV. The effect of antibody on HIV infection is analyzed. The production and removal rates of the ten compartments of the model are given by general nonlinear functions which satisfy reasonable conditions. Nonnegativity and ultimately boundedness of the solutions are proven. Using the Lyapunov method, the global stability of the equilibria of the model is proven. Numerical simulations of the system are provided to confirm the theoretical results. We have shown that the antibodies can play a significant role in controlling the HIV infection, but it cannot clear the HIV particles from the plasma. Moreover, we have demonstrated that the intracellular time delay plays a similar role as the Highly Active Antiretroviral Therapies (HAAT) drugs in eliminating the HIV particles.


2020 ◽  
Vol 295 (35) ◽  
pp. 12449-12460
Author(s):  
Masatoshi Kakizaki ◽  
Yuichiro Yamamoto ◽  
Motoyuki Otsuka ◽  
Kouichi Kitamura ◽  
Masatoshi Ito ◽  
...  

Hepatitis B, a viral infection that affects the liver, is thought to affect over 257 million people worldwide, and long-term infection can lead to life-threatening issues such as cirrhosis or liver cancer. Chronic hepatitis B develops by the interaction between hepatitis B virus (HBV) and host immune response. However, questions of how HBV-infected cells thwart immune system defenses remain unanswered. Extracellular vesicles (EVs) are used for cellular communication, carrying cargoes such as RNAs, proteins, and lipids and delivering them intracellularly after being endocytosed by target cells. HBV-infected liver cells secrete several types of EVs into body fluids such as complete and incomplete virions, and exosomes. We previously demonstrated that monocytes that incorporated EVs moved to immunoregulatory phenotypes via up-regulation of PD-L1, an immunocheckpoint molecule, and down-regulation of CD69, a leukocyte activation molecule. In this study, we transfected mice with HBV using hydrodynamic injection and studied the effects of EVs secreted by HBV-infected liver cells. EVs secreted from cells with HBV replication strongly suppressed the immune response, inhibiting the eradication of HBV-replicating cells in the mice transfected with HBV. EVs were systemically incorporated in multiple organs, including liver, bone marrow (BM), and intestine. Intriguingly, the BM cells that incorporated EVs acquired intestinal tropism and the dendritic cell populations in the intestine increased. These findings suggest that the EVs secreted by HBV-infected liver cells exert immunosuppressive functions, and that an association between the liver, bone marrow, and intestinal tract exists through EVs secreted from HBV-infected cells.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Can Jin ◽  
Peipei Wu ◽  
Linli Li ◽  
Wenrong Xu ◽  
Hui Qian

Exosomes are nanometer-sized small EVs coated with bilayer structure, which are released by prokaryotic and eukaryotic cells. Exosomes are rich in a variety of biologically active substances, such as proteins, nucleotides, and lipids. Exosomes are widely present in various body fluids and cell culture supernatants, and it mediates the physiological and pathological processes of the body through the shuttle of these active ingredients to target cells. In recent years, studies have shown that exosomes from a variety of cell sources can play a beneficial role in acute and chronic kidney disease. In particular, exosomes derived from mesenchymal stem cells have significant curative effects on the prevention and treatment of kidney disease in preclinical trials. Besides, some encapsulated substances are demonstrated to exert beneficial effects on various diseases, so they have attracted much attention. In addition, exosomes have extensive sources, stable biological activity, and good biocompatibility and are easy to store and transport; these advantages endow exosomes with superior diagnostic value. With the rapid development of liquid biopsy technology related to exosomes, the application of exosomes in the rapid diagnosis of kidney disease has become more prominent. In this review, the latest development of exosomes, including the biosynthesis process, the isolation and identification methods of exosomes are systematically summarized. The utilization of exosomes in diagnosis and their positive effects in the repair of kidney dysfunction are discussed, along with the specific mechanisms. This review is expected to be helpful for relevant studies and to provide insight into future applications in clinical practice.


2022 ◽  
Vol 12 ◽  
Author(s):  
Maria A. Navarrete-Muñoz ◽  
Carlos Llorens ◽  
José M. Benito ◽  
Norma Rallón

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.


2019 ◽  
Vol 20 (22) ◽  
pp. 5527 ◽  
Author(s):  
Tünde Szatmári ◽  
Rita Hargitai ◽  
Géza Sáfrány ◽  
Katalin Lumniczky

Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.


2021 ◽  
Vol 22 (10) ◽  
pp. 5366
Author(s):  
Ornella Urzì ◽  
Stefania Raimondo ◽  
Riccardo Alessandro

The scientific interest in the beneficial properties of natural substances has been recognized for decades, as well as the growing attention in extracellular vesicles (EVs) released by different organisms, in particular from animal cells. However, there is increasing interest in the isolation and biological and functional characterization of these lipoproteic structures in the plant kingdom. Similar to animal vesicles, these plant-derived extracellular vesicles (PDEVs) exhibit a complex content of small RNAs, proteins, lipids, and other metabolites. This sophisticated composition enables PDEVs to be therapeutically attractive. In this review, we report and discuss current knowledge on PDEVs in terms of isolation, characterization of their content, biological properties, and potential use as drug delivery systems. In conclusion, we outline controversial issues on which the scientific community shall focus the attention shortly.


2021 ◽  
Vol 22 (7) ◽  
pp. 3374
Author(s):  
Simone Lipinski ◽  
Katharina Tiemann

Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. In cancer, the content of EVs derived from tumor cells is altered and can induce oncogenic reprogramming of target cells. As a result, tumor-derived EVs compromise antitumor immunity and promote cancer progression and spreading. However, this pro-oncogenic phenotype is constantly being challenged by EVs derived from the local tumor microenvironment and from remote sources. Here, we summarize the role of EVs in the tumor–immune cross-talk that includes, but is not limited to, immune cells in the tumor microenvironment. We discuss the potential of remotely released EVs from the microbiome and during physical activity to shape the tumor–immune cross-talk, directly or indirectly, and confer antitumor activity. We further discuss the role of proinflammatory EVs in the temporal development of the tumor–immune interactions and their potential use for cancer diagnostics.


Sign in / Sign up

Export Citation Format

Share Document