Synthetic Drug Delivery Systems Research Articles

Recent Progress in Phage-Based Nanoplatforms for Tumor Therapy.

Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.

Targeted drug delivery system inspired by macropinocytosis.

Macropinocytosis is a widely-observed and evolutionarily-conserved endocytic process found in the eukaryotic cells. In comparison to other endocytic routes, macropinocytosis allows for the internalization of greater quantities of fluid-phase drugs, making it an attractive avenue for drug delivery. Recent evidence showed that various drug delivery systems can be internalized through macropinocytosis. Utilizing macropinocytosis may therefore provide a new avenue for targeted intracellular delivery. In this review, we provide an overview into the origins and distinctive properties of macropinocytosis, summarize the roles of macropinocytosis under healthy and pathological settings. Furthermore, we highlight the biomimetic and synthetic drug delivery systems that employ macropinocytosis as the primary internalization mechanism. To facilitate the clinical applications of these drug delivery systems, additional research can be conducted to enhance the cell-type selectivity of macropinocytosis, the control of drug release at the target, and the prevention of potential toxicity. The rapidly emerging field of macropinocytosis-based targeted drug delivery and therapies holds great potential to drastically increase the efficiency and specificity of drug delivery.

Targeting the central nervous system: From synthetic nanoparticles to extracellular vesicles-Focus on Alzheimer's and Parkinson's disease.

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are an accelerating global health problem as life expectancy rises worldwide. Despite their significant burden in public health systems to date, the existing treatments only manage the symptoms without slowing down disease progression. Thus, the ongoing neurodegenerative process remains untreated. Moreover, the stronghold of the brain-the blood-brain barrier (BBB)-prevents drug penetrance and dwindles effective treatments. In the last years, nanotechnology-based drug delivery systems (DDS) have become a promising approach to target and treat these disorders related to the central nervous system (CNS). PLGA based nanoparticles (NPs) were the first employed DDS for effective drug delivery. However, the poor drug loading capacity and localized immunogenicity prompted the scientific community to move to another DDS such as lipid-based NPs. Despite the lipid NPs' safety and effectiveness, their off-target accumulation together with the denominated CARPA (complement activation-related pseudo allergy) reaction has limited their complete clinical translation. Recently, biological NPs naturally secreted by cells, termed as extracellular vesicles (EVs) have emerged as promising more complex biocompatible DDS. In addition, EVs act as dual players in NDs treatment, as a "cell free" therapy themselves, as well as new biological NPs with numerous characteristics that qualify them as promising carriers over synthetic DDS. The present review aims to display advantages, drawbacks, current limitations and future prospective of the previously cited synthetic and biological DDS to enter the brain and treat one of 21st century most challenging diseases, NDs. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Genetically engineered bacteria: a new frontier in targeted drug delivery.

Genetically engineered bacteria (GEB) have shown significant promise to revolutionize modern medicine. These engineered bacteria with unique properties such as enhanced targeting, versatility, biofilm disruption, reduced drug resistance, self-amplification capabilities, and biodegradability represent a highly promising approach for targeted drug delivery and cancer theranostics. This innovative approach involves modifying bacterial strains to function as drug carriers, capable of delivering therapeutic agents directly to specific cells or tissues. Unlike synthetic drug delivery systems, GEB are inherently biodegradable and can be naturally eliminated from the body, reducing potential long-term side effects or complications associated with residual foreign constituents. However, several pivotal challenges such as safety and controllability need to be addressed. Researchers have explored novel tactics to improve their capabilities and overcome existing challenges, including synthetic biology tools (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) and bioinformatics-driven design), microbiome engineering, combination therapies, immune system interaction, and biocontainment strategies. Because of the remarkable advantages and tangible progress in this field, GEB may emerge as vital tools in personalized medicine, providing precise and controlled drug delivery for various diseases (especially cancer). In this context, future directions include the integration of nanotechnology with GEB, the focus on microbiota-targeted therapies, the incorporation of programmable behaviors, the enhancement in immunotherapy treatments, and the discovery of non-medical applications. In this way, careful ethical considerations and regulatory frameworks are necessary for developing GEB-based systems for targeted drug delivery. By addressing safety concerns, ensuring informed consent, promoting equitable access, understanding long-term effects, mitigating dual-use risks, and fostering public engagement, these engineered bacteria can be employed as promising delivery vehicles in bio- and nanomedicine. In this review, recent advances related to the application of GEB in targeted drug delivery and cancer therapy are discussed, covering crucial challenging issues and future perspectives.

Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications.

Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.

Chemische Ansätze für synthetische Wirkstofftransportsysteme für systemische Anwendungen

AbstractSchlechte Wasserlöslichkeit und geringe Bioverfügbarkeit von pharmazeutischen Wirkstoffen (APIs) sind die Hauptursache für Verzögerungen in der pharmazeutischen Industrie und stellen eine große Hürde für die Entwicklung neuer Arzneimittel dar. Der Transport von Arzneimitteln ist nach wie vor die größte Herausforderung für die Anwendung niedermolekularer Medikamente und Biopharmazeutika. Die drei Herausforderungen für synthetische Transportsysteme sind: (i) Kontrolle über die Wirkstoffverteilung und Clearance im Blut, (ii) Solubilisierung schlecht wasserlöslicher Wirkstoffe und (iii) selektive Akkumulation in bestimmten Geweben. Obwohl viele Polymer‐basierte Systeme die ersten beiden Anforderungen erfüllen und in die klinische Praxis umgesetzt wurden, hat bisher noch kein zielgerichtetes, synthetisches Abgabesystem den Markt erreicht. Dieser Aufsatz soll einen Überblick über die Herausforderungen und Anforderungen zur Entwicklung und Umsetzung neuer Polymer‐basierter Darreichungssysteme geben. Hauptaugenmerk liegt hierbei auf den chemischen Ansätzen für die Darreichung von Wirkstoffen für systemische Anwendungen.

Dual responsive molecularly imprinted polymers based on UiO-66-DOX for selective targeting tumor cells and controlled drug release

The preparation of synthetic drug delivery systems free of antibody modifications that can effectively recognize tumor sites and control drug delivery is essential for cancer therapy. In this study, UiO-66 metal–organic framework (MOF) modified with amino and phenylboronic acid groups was used as substrate to load the anti-cancer drug doxorubicin (DOX). Then a molecularly imprinted polymer (UiO-66-DOX@MIP) with sialic acid (SA) as the template molecule was further prepared on the surface of the synthesized nanoparticles using surface molecular imprinting technique (MIT). This polymer combines the excellent properties of UiO-66 and molecularly imprinted polymer (MIP). It was simple to prepare, economical and easy to obtain, and had a regular morphology. UiO-66-DOX@MIP containing molecularly imprinted binding sites that match the template molecule SA, could specifically recognize target tumor cells. The imprinted layer prevented drug leakage in normal body fluids while degrading and drug release under tumor microenvironment, with pH and glutathione (GSH) dual-responsive drug release properties. The UiO-66-DOX@MIP showed excellent biocompatibility and great cellular uptake efficiency to cancer cells without influence of interfering substances.

Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery.

The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.

Nucleic Acid Delivery with Red-Blood-Cell-Based Carriers.

Gene therapy has the potential to become a staple of 21st-century medicine. However, to overcome the limitations of existing gene-delivery therapies, that is, poor stability and inefficient and delivery and accumulation of nucleic acids (NAs), safe drug-delivery systems (DDSs) allowing the prolonged circulation and expression of the administered genes in vivo are needed. In this review article, the development of DDSs over the past 70 years is briefly described. Since synthetic DDSs can be recognized and eliminated as foreign substances by the immune system, new approaches must be found. Using the body’s own cells as DDSs is a unique and exciting strategy and can be used in a completely new way to overcome the critical limitations of existing drug-delivery approaches. Among the different circulatory cells, red blood cells (RBCs) are the most abundant and thus can be isolated in sufficiently large quantities to decrease the complexity and cost of the treatment compared to other cell-based carriers. Therefore, in the second part, this article describes 70 years of research on the development of RBCs as DDSs, covering the most important RBC properties and loading methods. In the third part, it focuses on RBCs as the NA delivery system with advantages and drawbacks discussed to decide whether they are suitable for NA delivery in vivo.

Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design.

Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another to modulate physiological and pathological processes. Due to their presumed biocompatibility and capacity to circumvent canonical delivery barriers encountered by synthetic drug delivery systems, EVs have attracted considerable interest as drug delivery vehicles. However, it is unclear which mechanisms and molecules orchestrate EV-mediated cargo delivery to recipient cells. Here, we review how EV properties have been exploited to improve the efficacy of small molecule drugs. Furthermore, we explore which EV surface molecules could be directly or indirectly involved in EV-mediated cargo transfer to recipient cells and discuss the cellular reporter systems with which such transfer can be studied. Finally, we elaborate on currently identified cellular processes involved in EV cargo delivery. Through these topics, we provide insights in critical effectors in the EV-cell interface which may be exploited in nature-inspired drug delivery strategies.

Glycoside phosphorylases for carbohydrate synthesis: An insight into the diversity and potentiality

Glycoside phosphorylases (GPs) are a major group of enzymes which catalyze the reversible formation and cleavage of glycosidic linkages, thus combining a dual functionality of both glycoside hydrolases (GHs) and glycosyltransferases (GTs). This unique advantage of reversibility, alongside with the strict regioselectivity, and the use of simple sugar phosphate donors, makes phosphorylases valuable catalysts in the synthesis of various carbohydrate structures, such as the synthesis of low-calorie sweeteners and valuable disaccharides, the synthesis of prebiotic compounds linked to health benefits, synthetic drug delivery systems and other physiological related structures, including, core components of N-linked glycans, O-linked mucin glycoproteins. Although these types of enzymes are still under-explored compared to the glycoside hydrolases and the glycosyltransferases, recently more discovered phosphorylases had been reported leading to more possibilities of synthesizing difficult glycosides. Herein we provide an overview of the distribution of GPs within the carbohydrate-active enzymes (CAZy) database, and the recent utilization of these enzymes for synthetic approaches of di- and oligosaccharides. • Glycoside phosphorylases (GPs) catalyze the reversible formation and cleavage of glycosidic linkages. • Glycoside phosphorylases have distinctive strict regioselectivity. • The reverse phosphorylsis functionality of GPs can be exploited to synthesize high value carbohydrate structures.

Extracellular vesicles as drug delivery systems: Why and how?

Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market. However, applications of such systems are limited due to inefficiency, cytotoxicity and/or immunogenicity. At the same time, the field of natural drug carrier systems has grown rapidly. One of the most prominent examples of such natural carriers are extracellular vesicles (EVs). EVs are cell-derived membranous particles which play important roles in intercellular communication. EVs possess a number of characteristics that qualify them as promising vehicles for drug delivery. In order to take advantage of these attributes, an in-depth understanding of why EVs are such unique carrier systems and how we can exploit their qualities is pivotal. Here, we review unique EV features that are relevant for drug delivery and highlight emerging strategies to make use of those features for drug loading and targeted delivery.

Temperature-Responsive Polymersomes of Poly(3-methyl-N-vinylcaprolactam)-block-poly(N-vinylpyrrolidone) To Decrease Doxorubicin-Induced Cardiotoxicity.

Despite being one of the most potent chemotherapeutics, doxorubicin (DOX) facilitates cardiac toxicity by irreversibly damaging the cardiac muscle as well as severely dysregulating the immune system and impairing the resolution of cardiac inflammation. Herein, we report synthesis and aqueous self-assembly of nanosized polymersomes from temperature-responsive poly(3-methyl-N-vinylcaprolactam)-block-poly(N-vinylpyrrolidone) (PMVC-PVPON) diblock copolymers and demonstrate their potential to minimize DOX cardiotoxicity compared to liposomal DOX. RAFT polymerization of vinylpyrrolidone and 3-methyl-N-vinylcaprolactam, which are structurally similar monomers but have drastically different hydrophobicity, allows decreasing the cloud point of PMVCm-PVPONn copolymers below 20 °C. The lower critical solution temperature (LCST) of the PMVC58-PVPONn copolymer varied from 19.2 to 18.6 and to 15.2 °C by decreasing the length of the hydrophilic PVPONn block from n = 98 to n = 65 and to n = 20, respectively. The copolymers assembled into stable vesicles at room temperature when PVPON polymerization degrees were 65 and 98. Anticancer drug DOX was entrapped with high efficiency into the aqueous PMVC58-PVPON65 polymersomal core surrounded by the hydrophobic temperature-sensitive PMVC shell and the hydrophilic PVPON corona. Unlike many liposomal, micellar, or synthetic drug delivery systems, these polymersomes exhibit an exceptionally high loading capacity of DOX (49%) and encapsulation efficiency (95%) due to spontaneous loading of the drug at room temperature from aqueous DOX solution. We also show that C57BL/6J mice injected with the lethal dose of DOX at 15 mg kg-1 did not survive the 14 day treatment, resulting in 100% mortality. The DOX-loaded PMVC58-PVPON65 polymersomes did not cause any mortality in mice indicating that they can be used for successful DOX encapsulation. The gravimetric analyses of the animal organs from mice treated with liposome-encapsulated DOX (Lipo-DOX) and PMVC58-PVPON65 polymersomes (Poly-DOX) revealed that the Lipo-DOX injection caused some toxicity manifesting as decreased body weight compared to Poly-DOX and saline control. Masses of the left ventricle of the heart, lung, and spleen reduced in the Lipo-DOX-treated mice compared to the nontoxic saline control, while no significant decrease of those masses was observed for the Poly-DOX-treated mice. Our results provide evidence for superior stability of synthetic polymersomes in vivo and show promise for the development of next-generation drug carriers with minimal side effects.

Терапевтический потенциал экзосом и их производных

В обзоре представлены современные данные о механизмах диагностики, планирования и оценки успешности терапии различных заболеваний с помощью экзосом, об использовании их как нанопереносчиков (т.е. нановезикул для эффективной доставки молекул). За последние годы разработано большое количество разных, в основном синтетических, систем доставки лекарственных средств, недостатками этих систем является плохая биосовместимость и органическая неспособность к высокоточной доставке загруженных веществ. По сравнению с синтетическими системами доставки лекарственных средств, экзосомы - вследствие своего естественного происхождения - могут обладать большими преимуществами, такими, как лучшая биосовместимость и повышенная устойчивость к разрушительному воздействию иммунной системы. Описана технология производства наноструктур, разработка и производство с помощью бионанотехнологий так называемых «полностью синтетических экзосомоподобных нановезикул», преимущества и недостатки этих методов. This review presents current data on mechanisms for diagnosis, planning, and evaluation of success in the treatment of various diseases using exosomes as nanocarriers (i.e., nanovesicles for efficient delivery of molecules). In recent years, a large number of different, mainly synthetic drug delivery systems has been developed. Disadvantages of these systems are poor biocompatibility and organic inability to deliver high-precision loaded substances. Compared with synthetic drug delivery systems, exosomes due to their natural origin may provide great advantages, such as better biocompatibility and increased resistance to detrimental effects of the immune system. This review describes in detail a technology of nanostructure production, the development and production of so-called fully synthetic exosome-like nanovesicles using bionanotechnology, and advantages and disadvantages of these methods.

Strategic design of extracellular vesicle drug delivery systems.

Extracellular vesicles (EVs), sub-micron vectors used in intercellular communication, have demonstrated great promise as natural drug delivery systems. Recent reports have detailed impressive in vivo results from the administration of EVs pre-loaded with therapeutic cargo, including small molecules, nanoparticles, proteins and oligonucleotides. These results have sparked intensive research interest across a huge range of disease models. There are, however, enduring limitations that have restricted widespread clinical and pharmaceutical adoption. In this perspective, we discuss these practical and biological concerns, critically compare the relative merit of EVs and synthetic drug delivery systems, and highlight the need for a more comprehensive understanding of in vivo transport and delivery. Within this framework, we seek to establish key areas in which EVs can gain a competitive advantage in order to provide the tangible added value required for widespread translation.

The influence of the grafting density of glycopolymers on the lectin binding affinity of block copolymer micelles

The integration of natural carbohydrates as ligands for the targeting of specific cell types into synthetic drug delivery systems such as polymer micelles has gained increasing attention, which is based on the expression of selective receptors or lectins in the cell membrane. While several structural aspects of this interaction are well-understood, only limited knowledge exists on the impact of the grafting density of sugar groups on this interaction. In the presented approach, we created core-shell-corona micelles with comparable size and shape, but a variable density of d-mannosylated chains sticking out from the surface, and investigated their interaction with the lectin concanavalin A (Con A). The polymers were synthesized using the reversible addition fragmentation chain transfer polymerization (RAFT) providing excellent control and narrow distributions for all materials. The blocks based on butyl acrylate and N-acryloyl morpholine form the core and shell of the micelles, respectively, while an additional d-mannosylated block, which forms the corona, is introduced applying a previously reported post-polymerisation functionalization of a reactive bromine precursor with α-d-thiomannose. Varying the ratios of the diblock and triblock polymers in the assembly process, the density of the d-mannosylated chains could easily be adjusted in this mixed micelles approach. All micelles revealed sizes of around 50 nm (estimated by light scattering and cryo-TEM) and similar morphologies, an aspect that is crucial for the direct evaluation of the influence of the grafting density on the binding affinity. The subsequent binding studies with the lectin Con A revealed a clear trend that binding affinity increases with increasing sugar content and a minimum of 10% of d-mannosylated chains is required for an effective and detectible aggregation. However, it is noteworthy that the full coverage of the micelles with sugar chains is detrimental for the binding to Con A and a significant reduction of the clustering rate was observed, while a ligand density of around 50–60% was favorable for the best interaction. These finding substantiate the importance of the ligand density for the design of targeting delivery systems.

Extracellular Vesicles in Neurodegenerative Diseases: A Double-Edged Sword.

Extracellular vesicles (EVs), a heterogenous group of membrane-bound particles, are virtually secreted by all cells and play important roles in cell-cell communication. Loaded with proteins, mRNAs, non-coding RNAs and membrane lipids from their donor cells, these vesicles participate in normal physiological and pathogenic processes. In addition, these sub-cellular vesicles are implicated in the progression of neurodegenerative disorders. Accumulating evidence suggests that intercellular communication via EVs is responsible for the propagation of key pathogenic proteins involved in the pathogenesis of amyotrophic lateral sclerosis, Parkinson's diseases, Alzheimer's diseases and other neurodegenerative disorders. For therapeutic perspective, EVs present advantage over other synthetic drug delivery systems or cell therapy; ability to cross biological barriers including blood brain barrier (BBB), ability to modulate inflammation and immune responses, stability and longer biodistribution with lack of tumorigenicity. In this review, we summarized the current state of EV research in central nervous system in terms of their values in diagnosis, disease pathology and therapeutic applications.

Remotely controlled red blood cell carriers for cancer targeting and near-infrared light-triggered drug release in combined photothermal chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus-responsive, RBC-based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near-infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light-induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC-based cancer cell targeted drug delivery and light-controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.

Remotely Controlled Red Blood Cell Carriers for Cancer Targeting and Near‐Infrared Light‐Triggered Drug Release in Combined Photothermal–Chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus‐responsive, RBC‐based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near‐infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light‐induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC‐based cancer cell targeted drug delivery and light‐controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.

Exosomes: potential model for complement-stealth delivery systems

AbstractExosomes are nature’s nanocarriers that transport biological information in humans. Their structural properties, origin and functions are making them interesting objects for the diagnosis of diseases, such as cancer, and also, as innovative tools for drug delivery. The interaction of exosomes with the immune system has been one of the focal points of interest; nevertheless their “stealth” properties helping to avoid adverse immune reactions are still not fully understood. In this review, after giving an overview of recent findings on the role of exosomes in disease pathogenesis and physiological functions, we focused on their interaction with the immune system and possibilities for clinical applications. The potential of exosomes of creating stealth nanoparticles that are better tolerated by the immune system than the presently available synthetic drug delivery systems represent a promising new approach in nanomedicine.