Exosome-based Drug Delivery Systems Research Articles

Exosome-based drug delivery systems for enhanced neurological therapeutics.

Exosomes are small extracellular vesicles naturally secreted by cells into body fluids, enriched with bioactive molecules such as RNAs, proteins, and lipids. These nanosized vesicles play a crucial role in physiological and pathological processes by facilitating intercellular communication and modulating cellular responses, particularly within the central nervous system (CNS). Their ability to cross the blood-brain barrier and reflect the characteristics of their parent cells makes exosomal cargo a promising candidate for biomarkers in the early diagnosis and clinical assessment of neurological conditions. This review offers a comprehensive overview of current knowledge on the characterization of mammalian-derived exosomes, their application as drug delivery systems for neurological disorders, and ongoing clinical trials involving exosome-loaded cargo. Despite their promising attributes, a significant challenge remains the lack of standardized isolation methods, as current techniques are often complex, costly, and require sophisticated equipment, affecting the scalability and affordability of exosome-based therapies. The review highlights the engineering potential of exosomes, emphasizing their ability to be customized for targeted therapeutic delivery through surface modification or conjugation. Future advancements in addressing these challenges and leveraging the unique properties of exosomes could lead to innovative and effective therapeutic strategies in neurology.

Milk-Derived Exosomes: Innovative Nanocarriers for Enhanced Anticancer Drug Delivery

This in-depth review examines the recently emerging field of using exosomes from milk as anticancer medication nanocarriers. It gives a summary of the most current developments, difficulties, and opportunities in this cutting-edge therapeutic strategy. Exosomes are found in many different body fluids and are considered a promising option for precision medicine due to their biocompatibility and innate cell-targeting abilities. These extracellular vesicles are nanoscale. The review commences with a comprehensive synopsis of the composition and biogenesis of exosomes derived from milk, highlighting their distinct membrane properties and capacity to transport cargo. Interestingly, these naturally occurring nanocarriers hold a variety of bioactive substances that can be precisely delivered as anticancer medications. These substances include proteins, lipids, and nucleic acids. Because dietary(poly) phenols are rapidly metabolized, their ability to prevent cancer is limited. Extracellular vesicles called exosomes may shield polyphenols from metabolism. Our objective was to evaluate the anticancer effects of free curcumin and resveratrol in breast cancer cell lines compared to their encapsulation in extracellular matrix derived from milk. Breast tissue was disposed of kinetically using rats. Curcumin and resveratrol were assessed using UPLC-QTOF-MS and GV-MS, respectively. Dietary polyphenols have a limited capacity to prevent cancer due to their rapid metabolism. Extracellular vesicles called exosomes may shield polyphenols from metabolism. Our goal was to assess in breast tissue. UPLC-QTOF-MS and GV-MS were used to evaluate curcumin and resveratrol, respectively. Curcumin and Resveratrol anticancer activity and bioavailability were improved by milk extracellular urea, which served as Trojan horses to get around the ABC-mediated chemoresistance of cancer cells. Exosomes derived from milk are being studied for their potential as carriers of therapeutic and diagnostic agents, emphasizing the potential benefits of personalized and precision medicine approaches to cancer treatment. The review also covers the challenges that the clinical translation of milk-derived exosome-based drug delivery systems currently faces, including scalability, standardization and safety profiles. The article's conclusion presents an optimistic view of how milk-derived exosomes will develop in the future in terms of anticancer medication delivery. The review highlights the revolutionary potential of using milk-derived exosomes, nature's nanocarriers, to advance the field toward more precise and effective cancer treatments, anticipating future advancements and emerging trends.

Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery.

Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

A comprehensive review of challenges and advances in exosome-based drug delivery systems.

Exosomes or so-called natural nanoparticles have recently shown enormous potential for targeted drug delivery systems. Several studies have reported that exosomes as advanced drug delivery platforms offer efficient targeting of chemotherapeutics compared to individual polymeric nanoparticles or liposomes. Taking structural constituents of exosomes, viz., proteins, nucleic acids, and lipids, into consideration, exosomes are the most promising carriers as genetic messengers and for treating genetic deficiencies or tumor progression. Unfortunately, very little attention has been paid to the factors like source, scalability, stability, and validation that contribute to the quality attributes of exosome-based drug products. Some studies suggested that exosomes were stable at around -80 °C, which is impractical for storing pharmaceutical products. Currently, no reports on the shelf-life and in vivo stability of exosome formulations are available. Exosomes are quickly cleared from blood circulation, and their in vivo distribution depends on the source. Considering these challenges, further studies are necessary to address major limitations such as poor drug loading, reduced in vivo stability, a need for robust, economical, and scalable production methods, etc., which may unlock the potential of exosomes in clinical applications. A few reports based on hybrid exosomes involving hybridization between different cell/tumor/macrophage-derived exosomes with synthetic liposomes through membrane fusion have shown to overcome some limitations associated with natural or synthetic exosomes. Yet, sufficient evidence is indispensable to prove their stability and clinical efficacy.

The Promise of Exosomes as Drug Delivery Systems

Exosomes are small extracellular vesicles that play a role in cell-to-cell communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids between cells. Over the past few years, there have been significant advances in utilizing exosomes as drug delivery systems due to their unique properties, including their ability to target specific cells and tissues. Especially advances in targeted delivery, nanoparticle incorporation, personalized medicine, cargo delivery, imaging, and tracking have excited the pharmaceutical community about their potential use in these areas. I briefly discuss the significance of exosomes in these areas or research interests. Natural Cargo Delivery: Exosomes naturally transport a variety of biomolecules, making them attractive vehicles for delivering drugs, nucleic acids (such as siRNA and miRNA), proteins, and even small molecules. Researchers are harnessing this inherent cargo delivery capability to load exosomes with therapeutic agents. Engineered Exosomes: Scientists are engineering exosomes to enhance their drug delivery capabilities. This includes modifying the surface of exosomes to display targeting ligands that can direct them to specific cell types or tissues, improving their stability, and optimizing their cargo-loading efficiency. Targeted Delivery: One of the key advantages of using exosomes for drug delivery is their potential for targeted delivery. By engineering exosomes to carry targeting molecules on their surface, researchers can selectively deliver therapeutic agents to specific cells or disease sites, minimizing off-target effects. Personalized Medicine: Exosomes can be isolated from a patient's cells (autologous exosomes), loaded with personalized therapies, and then re-administered to the patient. This personalized approach holds promise for tailoring treatments to individual patients' needs. Imaging and Tracking: Exosomes can be labeled with imaging agents to track their distribution and uptake in vivo. This information is crucial for understanding the pharmacokinetics and biodistribution of exosome-based drug delivery systems. Nanoparticle Incorporation: Exosomes can be loaded with nanoparticles, such as liposomes or polymer-based carriers, to increase their cargo capacity and control drug release kinetics. This combination allows for synergistic benefits of both exosome-mediated and nanoparticle-based drug delivery. Clinical Translation: Clinical trials involving exosome-based therapies are underway for various diseases, including cancer and neurodegenerative disorders. These trials provide valuable insights into the safety, efficacy, and challenges associated with exosome-based drug delivery in humans. Regulatory Considerations: The field of exosome-based drug delivery is also evolving in terms of regulatory considerations. Regulatory agencies are working to establish guidelines and standards for developing and approving exosome-based therapies. Exosome Isolation and Purification Techniques: Advances in exosome isolation and purification methods are critical for obtaining high-quality and consistent exosome preparations for drug delivery studies. Improved techniques contribute to the reproducibility and reliability of exosome-based therapies. Disease-Specific Cargo: Exosomes derived from specific cell types or disease models can be isolated and used as delivery vehicles for disease-specific cargo, including diagnostic biomarkers and therapeutic agents. This enables precise delivery to disease-affected cells. Combination Therapies: Researchers are exploring the potential of using exosomes to deliver combination therapies, where multiple therapeutic agents are loaded into a single exosome to achieve synergistic effects. The study of exosomes as drug delivery systems is rapidly advancing and holds great promise for improving the targeted delivery of therapeutic agents, reducing side effects, and enabling personalized medicine approaches. However, scalability, cargo loading efficiency, safety, and regulatory approval challenges still need to be addressed as the field progresses.

Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery

BackgroundRecently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production. Because the active-targeting ability of drug carriers is essential to maximize therapeutic efficacy and minimize side effects, precise membrane functionalization strategies are required to enable tissue-specific delivery of milk exosomes with difficulty in post-isolation modification.MethodsIn this study, the membrane functionalization of a milk exosome platform modified using a simple post-insertion method was examined comprehensively. Exosomes were engineered from bovine milk (mExo) with surface-tunable modifications for the delivery of tumor-targeting doxorubicin (Dox). The surface modification of mExo was achieved through the hydrophobic insertion of folate (FA)-conjugated lipids.ResultsWe have confirmed the stable integration of functionalized PE-lipid chains into the mExo membrane through an optimized post-insertion technique, thereby effectively enhancing the surface functionality of mExo. Indeed, the results revealed that FA-modified mExo (mExo-FA) improved cellular uptake in cancer cells via FA receptor (FR)-mediated endocytosis. The designed mExo-FA selectively delivered Dox to FR-positive tumor cells and triggered notable tumor cell death, as confirmed by in vitro and in vivo analyses.ConclusionsThis simple and easy method for post-isolation modification of the exosomal surface may be used to develop milk-exosome-based drug delivery systems.Graphical

Exosomes as drug delivery system in gastrointestinal cancer.

Gastrointestinal cancer is one of the most common malignancies with relatively high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived from most cells and widely distributed in body fluids. They are natural endogenous nanocarriers with low immunogenicity, high biocompatibility, and natural targeting, and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins, lipids, and other bioactive components, which can play a role in information transmission and regulation of cellular physiological and pathological processes during the progression of gastrointestinal cancer. In this paper, the role of exosomes in gastrointestinal cancers is briefly reviewed, with emphasis on the application of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the challenges faced by exosome-based drug delivery systems are discussed.

Exosome-based drug delivery systems for the treatment of diabetes and its complications: current opinion

Diabetes medication is based on controlling blood glucose and delaying the onset of related complications and is not a complete cure for diabetes. Conventional drug therapy fails to stop progressive islet β cell failure in diabetic patients. Recent studies have shown that "exosome-based therapy" holds great promise in treating diabetes and its complications. Exosomes are small vesicles that are stable in the bloodstream and can effectively deliver therapeutic drugs to specific tissues or organs through intercellular communication. Using exosomes as carriers for drug delivery offers several advantages. This review summarizes the benefits of exosomal drug delivery systems, drug loading methods, and their applications in treating diabetes and its complications. However, there are still challenges to overcome in using exosomal drug delivery systems, such as large-scale production, assessing the contents of exosomes, and monitoring the safety and effectiveness of the treatment in vivo. In conclusion, this review proposes the therapeutical potential of exosomes as drug carriers for developing novel drugs to provide new strategies for treating diabetes and its complications.

Origin and Composition of Exosomes as Crucial Factors in Designing Drug Delivery Systems

Exosomes are a subpopulation of extravascular vesicles with a diameter of 30–150 nm. They are cellular-communication mediators, often reaching very distant organism tissues. Information is transferred by exosomal cargo, composed of a wide variety of macromolecules such as nucleic acids, proteins, and lipids. Exosomes possess natural specific cell targeting properties that are desirable in designing targeted macromolecules (DNA and RNA) and drug delivery systems (doxorubicin, paclitaxel, and taxol). In this context, exosomes can be defined as bio-derived drug transporting and protecting devices for the treatment of bacterial (toxoplasmosis and salmonellosis), viral (AIDS and hepatitis B), and cancer (lung, pancreatic, colon, brain, and breast) diseases. Extensive research proves that exosomes’ natural cargo can double-act, both increasing and decreasing the disease severity. In this case, the exosomes need to be prepared, namely, their origin and their cargo need to be screened and known. Thus, appropriate methods for intact and price-effective exosome isolation are needed with further exosome properties description. Among many utilized isolation methods, the most common are ultracentrifugation, polymer-based precipitation, and affinity precipitation-isolation systems, but novel microfluidic methods compromising high efficacy and purity are being developed. In this review, we state the current knowledge and trends in exosome-based drug delivery systems.

Research Progress in Exosome-Based Nanoscale Drug Carriers in Tumor Therapies.

Current antitumor treatment methods have several reported limitations, including multidrug resistance and serious adverse reactions. Targeted drug delivery systems are effective alternatives that can help healthcare providers overcome these limitations. Exosomes can serve as a natural nanoscale drug delivery system, with the advantages of high biocompatibility, low immunogenicity, and efficient tumor targetability. In this paper, we discuss the biological characteristics of exosomes, summarize the drug-carrying mechanisms of exosome-based drug delivery systems, and examine the potential role and applicability of exosomes in clinical tumor treatment approaches. This review can be used as a guideline for the future development of exosome-based delivery systems in clinical precision tumor treatment.

Exosome-based drug delivery systems in cancer therapy

Exosome, which is a kind of extracellular vesicles with size around 40-160 nm, plays an important role in cell-to-cell communication in multiple diseases. Especially in tumor microenvironment, exosomes are the important pathway to transit proteins, nucleic acids and small molecules between different kinds of cells. Based on these characteristics, exosomes are served as both therapeutic agents and drug delivery systems in cancer therapy. In this review, the applications of exosomes as drug delivery systems in cancer therapy were summarized and classified according to the cell source of the exosomes, including normal cells, immune cells and tumor cells. Different modifications of exosomes and drug loading methods were presented. Finally, some challenges that hindered the clinical translation of exosomes were also discussed.

Exosomes as Drug Carriers in Anti-Cancer Therapy.

Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.

Exosome-based drug delivery systems and their therapeutic applications.

In the past few decades, scientists have actively worked on developing effective drug delivery systems (DDSs) as means to control life-threatening diseases and challenging illnesses. In order to develop such DDSs, nanobiotechnological strategies have been introduced, and many nanomaterial-based DDS platforms have been proposed. Among these nanomaterials, DDSs based on exosomes and hybrids of exosomes have been focused upon and developed due to their low toxicity, high bioactivity, and biocompatibility. In this review, we describe the processes involved in drug loading into exosomes and the surface modification of exosomes with treatment agents. Furthermore, we describe the synthesis methods of hybrid exosomes with organic or inorganic nanoparticles. Moreover, we focus on the effective therapeutic applications of exosome-based DDSs against various diseases. In conclusion, we show that exosomes and hybrids of exosomes show excellent drug carrier potential and capacity.

Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy.

Simple SummaryExosomes derived from various sources can deliver therapeutic agents such as small molecule drugs, nucleic acids, and proteins to cancer cells by passive or active targeting. These exosomes can encapsulate drugs inside the exosomes, extending drug half-life and increasing drug release stability. In addition, exosomes are highly biocompatible due to their endogenous origin and can be used as nanocarriers for tissue-specific targeted delivery. This review discusses recent advances in exosome-based drug delivery for cancer therapy.Exosomes are a class of extracellular vesicles, with a size of about 100 nm, secreted by most cells and carrying various bioactive molecules such as nucleic acids, proteins, and lipids, and reflect the biological status of parent cells. Exosomes have natural advantages such as high biocompatibility and low immunogenicity for efficient delivery of therapeutic agents such as chemotherapeutic drugs, nucleic acids, and proteins. In this review, we introduce the latest explorations of exosome-based drug delivery systems for cancer therapy, with particular focus on the targeted delivery of various types of cargoes.

Drug loading techniques for exosome-based drug delivery systems.

Exosomes are bilayer membrane-coated extracellular vesicles measuring between 40 and 100 nm in diameter. As a natural carrier, exosomes have the advantages of low immunogenicity, high stability in blood, and direct delivery of drugs to cells. Exosomes can be transported between cells and thus are conducive to the exchange of substances and information between cells. They change the functional state of recipient cells by loading exogenous drugs (e.g., small-molecule drugs, transmembrane proteins, and nucleic acid drugs). The key to using exosomes as drug carriers is the effective loading of exogenous drugs into exosomes; however, this task poses a challenge in studying the functionalization of exosomes as drug carriers. Currently, sonication, electroporation, transfection, incubation, extrusion, saponin-assisted loading, transgenesis, freeze-thaw cycles, thermal shock, pH gradient method, and hypotonic dialysis have been applied to load these drugs into exosomes. This review aims to provide an overview of the advantages and disadvantages of various drug loading technologies for exosomes.

Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus.

Exosomes, nanometer-sized lipid-bilayer-enclosed extracellular vesicles (EVs), have attracted increasing attention due to their inherent ability to shuttle proteins, lipids and genes between cells and their natural affinity to target cells. Their intrinsic features such as stability, biocompatibility, low immunogenicity and ability to overcome biological barriers, have prompted interest in using exosomes as drug delivery vehicles, especially for gene therapy. Evidence indicates that exosomes play roles in both immune stimulation and tolerance, regulating immune signaling and inflammation. To date, exosome-based nanocarriers delivering small molecule drugs have been developed to treat many prevalent autoimmune diseases. This review highlights the key features of exosomes as drug delivery vehicles, such as therapeutic cargo, use of targeting peptide, loading method and administration route with a broad focus. In addition, we outline the current state of evidence in the field of exosome-based drug delivery systems in systemic lupus erythematosus (SLE), evaluating exosomes derived from various cell types and engineered exosomes.

Prospects and challenges of exosomes as drug delivery systems

Exosomes are nanoscale vectors with a diameter of 30~100 nm secreted by living cells, and they are important media for intercellular communication. Recent studies have demonstrated that exosomes can not only serve as biomarkers for diagnosis, but also have great potential as natural drug delivery vectors. Exosomes can be loaded with therapeutic cargos, including small molecules, proteins, and oligonucleotides. Meanwhile, the unique biological compatibility, high stability, and tumor targeting of exosomes make them attractive in future tumor therapy. Though exosomes can effectively deliver bioactive materials to receptor cells, there is a wide gap between our current understanding of exosomes and their application as ideal drug delivery systems. In this review, we will briefly introduce the function and composition of exosomes, and mainly summarize the potential advantages and challenges of exosomes as drug carriers. Finally, this review is expected to provide new ideas for the development of exosome-based drug delivery systems.

Exosomes as Drug Delivery Vehicles for Cancer Treatment

Exosomes are nanoscale extracellular vesicles that encapsulate a diverse range of biomolecules such as nucleic acids, proteins, and lipids. They are involved in several biological processes and mediate intracellular communication. Recent reports that they exhibit unique traits in pathological conditions have generated significant interest in employing them as diagnostic and therapeutic tools. Particularly, their potential to serve as drug delivery vehicles for the treatment of cancer and other diseases has been explored in numerous studies. This manuscript reviews recent developments in the field and discusses important considerations for further refinement of this approach and realization of more effective exosome-based drug delivery systems.

Aptamer-guided extracellular vesicle theranostics in oncology.

In the past decade, the study of exosomes, nanosized vesicles (50-150 nm) released into the extracellular space via the fusion of multivesicular bodies with the plasma membrane, has burgeoned with impressive achievements in theranostics applications. These nanosized vesicles have emerged as key players in homeostasis and in the pathogenesis of diseases owing to the variety of the cargos they can carry, the nature of the molecules packaged inside the vesicles, and the robust interactions between exosomes and target cells or tissues. Accordingly, the development of exosome-based liquid biopsy techniques for early disease detection and for monitoring disease progression marks a new era of precision medicine in the 21st century. Moreover, exosomes possess intrinsic properties - a nanosized structure and unique "homing effects" - that make them outstanding drug delivery vehicles. In addition, targeted exosome-based drug delivery systems can be further optimized using active targeting ligands such as nucleic acid aptamers. Indeed, the aptamers themselves can function as therapeutic and/or diagnostic tools based on their attributes of unique target-binding and non-immunogenicity. This review aims to provide readers with a current picture of the research on exosomes and aptamers and their applications in cancer theranostics, highlighting recent advances in their transition from the bench to the clinic.

Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy.

Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles.Methods: In this study, a pH-responsive superparamagnetic nanoparticles cluster (denoted as SMNC)-based method was developed for the precise and mild separation of blood TfR+ exosomes. Briefly, multiple superparamagnetic nanoparticles (SPMNs) labeled with transferrins (Tfs) could precisely bind to blood TfR+ exosomes to form an exosome-based cluster due to the specific recognition of TfR by Tf. They could realize the precise magnetic separation of blood TfR+ exosomes. More importantly, the pH-responsive dissociation characteristic of Tf and TfR led to the mild collapse of clusters to obtain pure blood TfR+ exosomes.Results: Blood TfR+ exosomes with high purity and in their original state were successfully obtained through the pH-responsive SMNC-based method. These can load Doxorubicin (DOX) with a loading capacity of ~10% and dramatically increase the tumor accumulation of DOX in tumor-bearing mice because of their innate passive-targeting ability. In addition, blood TfR+ exosomes changed the biodistribution of DOX leading to the reduction of side effects. Compared with free DOX, DOX-loaded blood TfR+ exosomes showed much better tumor inhibition effects on tumor-bearing mice.Conclusion: Taking advantage of the pH-responsive binding and disaggregation characteristics of Tf and TfR, the SMNC-based method can precisely separate blood TfR+ exosomes with high purity and in their original state. The resulting blood TfR+ exosomes showed excellent bio-safety and enable the efficient delivery of chemotherapeutics to tumors, facilitating the clinical translation of exosome-based drug delivery systems.