Extracellular vesicles （EVs） have attracted much attention as new therapeutic agents and DDS carriers. In recent years, there has been a great deal of progress in the development of technologies for modifying EVs to acquire new functions. In this paper, we summarize the current challenges for DDS applications of EVs and introduce recent research on the functionalization of EVs. In particular, we review the research on extracellular vesicle hybrid engineering, which aims to impart functions by conjugation and complexation of various functional molecules, nanocarriers, and inorganic nanoparticles with EVs.
Extracellular vesicles （EVs） exert producing cell-derived functions so that development of EV-based therapeutics is expected. There are a variety of immunotherapies using EVs. Main ones are vaccine therapy to induce antigen-specific immune response and anti-inflammatory therapy using EVs isolated from mesenchymal stem cells and other immunomodulatory cells. In recent years, results suggesting the possibility of immunotherapy utilizing EVs as vesicles secreted by cells and other characteristics unique to EVs have also been reported. In this article, we will introduce the current status of immunotherapy using EVs and discuss the future possibilities of EV-based immunotherapy.
Exosomes are a type of extracellular vesicles （EVs） and have an in vivo molecular transport system. Nucleic acids and proteins （e.g., microRNAs, mRNAs） are encapsulated in the vesicle and secreted from cells, taken up by recipient cells, and then the cargo of exosomes are released intracellularly. Therefore, exosomes are highly expected as naturally occurring molecular carriers for drug delivery system （DDS）. We have recently developed a novel DDS “ExomiR-Tracker“ that can deliver anti-microRNA oligonucleotide to exosome-recipient cells associated with exosome by using arginized anti-exosome antibody. In this review, we introduce the characterization of exosomal surface antigens and summarize the technologies that utilize the proteins and lipids on the surface of exosome membranes.
In recent years, expectations have been raised for the emergence of new diagnostic and therapeutic technologies based on extracellular vesicles. On the other hand, it is not easy to measure and manipulate a heterogeneous population of particles with diameters ranging from tens of nm to 100 nm, and there is a need to establish fundamental technologies that support the reliability, safety, and standardization of exosome medicine. For example, the dynamic light scattering method is widely used to measure the size of nanoparticles, but in this method, instead of measuring individual particles, the particle population is irradiated with laser light, and the autocorrelation function of the temporal variation of the scattered light intensity caused by the Brownian motion of the particles is measured and analyzed to obtain the particle size distribution. Single-particle measurements can avoid this problem, but the technical difficulty of detecting and manipulating particles as small as several tens of nanometers is high, and a new breakthrough is needed. Therefore, we have been developing a platform technology to enable single particle measurement of exosomes by applying biodevice technologies such as microfluidic devices and array of chips. In this paper, we introduce the recent development trend of electrophoresis chip for zeta potential measurement, nanoparticle separation device, and exosome array chip, and discuss the development trend and prospects of exosome evaluation and separation technology.
Liquid biopsy is a method that is expected to be able to detect and track the cancers using blood, urine, saliva and other body fluids. The advantages of liquid biopsy are that it is extremely minimally invasive compared to tissue biopsies, and that it is easy to perform the repeated and frequent tests that are necessary for long-term tracking. Recently, extracellular vesicles （EVs） have been added to the list of biological materials to be analyzed by liquid biopsy. In this paper, we introduce the comprehensive analysis of microRNAs contained in EVs in urine using nanowire devices and AI, and its application to cancer detection.
Cellular senescence is an important tumor suppression mechanism caused by various stresses. Senescent cells secrete a large number of inflammatory proteins, which is called as senescence-associated secretory phenotype （SASP）. Inflammatory SASP factors secreted from senescent cells induce chronic inflammation in the surrounding tissues, thereby causing age-related diseases. Recently, it has been shown that the secretion of small extracellular vesicle （sEV） is enhanced in senescent cells, acting as one of tumorigenic SASP factors. This article reviews the basic molecular mechanisms of sEV biogenesis in senescent cells and the latest findings on the biological function of sEV secreted from senescent cells. We also discuss the possibilities for clinical application of sEV in the field of aging research.
It has been reported that membrane vesicles（MV）, which are composed of cell membranes of every cell, exist among all life in each kingdom. All gram-negative and positive bacteria produce membrane vesicles. Cell response, mediated by bacterial membrane vesicles, also exists between animals/plants and bacteria, not only between bacterial cells. The roles and physiological functions of MV have been attracting attention in recent years. Active cell death is involved in the formation of MV, leading to their diversity.