Natural Delivery Systems Research Articles

Edible Layer-by-Layer Electrostatic Adsorption Nano and Microcapsules Based on Plant Proteins as Natural Bioactive Delivery Systems: A Review

Edible Layer-by-Layer Electrostatic Adsorption Nano and Microcapsules Based on Plant Proteins as Natural Bioactive Delivery Systems: A Review

Effect of ultrasonic treatment on the structure and emulsification properties of soybean isolate protein-hyaluronic acid complexes and the stability of their loaded astaxanthin emulsions

The purpose of this work was to prepare an astaxanthin emulsion stabilized by a soybean isolate protein (SPI)-hyaluronic acid (HA) complex and to investigate its protective effect on astaxanthin. In order to examine the impact of various ultrasonic energies (0 W–300 W) on the structural characteristics of the complex and the stability of the emulsion, the SPI-HA complex was created via ultrasonography. The findings demonstrated that ultrasonication may had an impact on the hydrophobic, electrostatic, and hydrogen bonding interactions between SPI and HA, which caused the protein structure to unfold and reveal the interior hydrophobic amino acid residues. Moreover, ultrasonication enhanced the emulsification qualities of SPI-HA complexes by lowering their average particle size. The rheological findings demonstrated that the emulsion's viscosity and energy storage modulus (G′) were considerably decreased by the ultrasonic treatment. The appearance of the emulsions and optical microscopy results further indicated that the emulsions prepared from SPI-HA had superior storage stability, pH stability, and light stability compared to pure SPI. SPI-HA exhibited superior emulsion stability and lower particle size at 150 W ultrasonic power. The AST incorporated in the emulsion was also well protected. The emulsion effectively slows down the degradation of AST. The findings of this study may help create more robust and natural emulsion delivery systems that guarantee the continuous or regulated release of lipophilic bioactive compounds.

MiR-29a-laden extracellular vesicles efficiently induced apoptosis through autophagy blockage in HCC cells

BackgroundIn spite of significant advancements in theraputic modalities for hepatocellular carcinoma (HCC), there is still a high annual mortality rate with a rising incidence. Major challenges in the HCC clinical managment are related to the development of therapy resistance, and evasion of tumor cells apoptosis which leading unsatisfactory outcomes in HCC patients. Previous investigations have shown that autophagy plays crucial role in contributing to drug resistance development in HCC. Although, miR-29a is known to counteract authophagy, increasing evidence revealed a down-regulation of miR-29a in HCC patients which correlates with poor prognosis. Beside, evidences showed that miR-29a serves as a negative regulator of autophagy in other cancers. In the current study, we aim to investigate the impact of miR-29a on the autophagy and apoptosis in HCC cells using extracellular vesicles (EVs) as a natural delivery system given their potential in the miRNA delivery both in vitro and in vivo. MethodHuman Wharton’s Jelly mesenchymal stromal cell-derived extracellular vesicles were lately isolated through 20,000 or 110,000 × g centrifugation (EV20K or EV110K, respectively), characterized by western blot (WB), scanning electron microscopy (SEM), and dynamic light scattering (DLS). miR-29a was subsequently loaded into these EVs and its loading efficiency was evaluated via RT-qPCR. Comprehensive in vitro and in vivo assessments were then performed on Huh-7 and HepG2 cell lines. ResultsEV20K-miR-29a treatment significantly induces cell apoptosis and reduces both cell proliferation and colony formation in Huh-7 and HepG2 cell lines. In addition, LC3-II/LC3-I ratio was increased while the expression of key autophagy regulators TFEB and ATG9A were downregulated by this treatment. These findings suggest an effective blockade of autophagy by EV20K-miR-29a leading to apoptosis in the HCC cell lines through concomitant targeting of critical mediators within each pathway.

Carotenoids encapsulated in natural flaxseed oil body: Different colloidal interfaces induce their behavior and stability disparity

Flaxseed oil bodies (FOBs) are being explored as natural plant-based delivery systems for the encapsulation and delivery of nutrients. However, there is currently a relatively poor understanding of their interfacial interaction and how this impacts delivery systems. In this study, β-carotene and lutein with far different molecular polarity were used to provide insights into their impacts on properties of FOB. In addition to the carotenoids (>93%) embedded and dissolved in the lipid core, they also interacted with the interfacial membrane components to impact the FOB properties. Raman showed the proportion of random coil and β-sheet in FOB-L (hydrophilic domain of interfacial protein) increased by 8% and 5% respectively, but remained almost unchanged in FOB-β, indicating lutein could interact with the polar exterior of interfacial membranes. Consistently, molecular dynamic simulations and spectroscopy analysis showed that lutein containing hydroxyl in β, ε-ionone ring was more likely to approach the outer hydrophilic regions of interfacial protein, while fatty soluble β-carotene interacted with hydrophobic region of inner membrane protein and phospholipid alkyl chain (close to oil). This difference in interfacial interactions induced significant discrepancies in the lipid oxidation, rheological behavior of carotenoid-FOB assemblies. Lutein was located at the outer edge where oxidation begins, making it more effective than β-carotene in improving the lipid oxidation stability of the FOB. Moreover, lutein therefore modulated interactions between oil droplets and altered the rheological properties of the FOB, whereas β-carotene had little effect. This study may facilitate the design of oil bodies-based delivery systems that have improved functional properties.

Plant-derived exosome-like nanoparticles for microRNA delivery in cancer treatment.

Plant-derived exosome-like nanoparticles (PELNs) are natural nanocarriers and effective delivery systems for plant microRNAs (miRNAs). These PELN-carrying plant miRNAs can regulate mammalian genes across species, thereby increasing the diversity of miRNAs in mammals and exerting multi-target effects that play a crucial role in diseases, particularly cancer. PELNs demonstrate exceptional stability, biocompatibility, and targeting capabilities that protect and facilitate the up-take and cross-kingdom communication of plant miRNAs in mammals. Primarily ingested and absorbed within the gastrointestinal tract of mammals, PELNs preferentially act on the intestine to regulate intestinal homeostasis through functional miRNA activity. The oncogenesis and progression of cancer are closely associated with disruptions in intestinal barriers, ecological imbalances, as well as secondary changes, such as abnormal inflammatory reactions caused by them. Therefore, it is imperative to investigate whether PELNs exert their anticancer effects by regulating mammalian intestinal homeostasis and inflammation. This review aims to elucidate the intrinsic crosstalk relationships and mechanisms of PELNs-mediated miRNAs in maintaining intestinal homeostasis, regulating inflammation and cancer treatment. Furthermore, serving as exceptional drug delivery systems for miRNAs molecules, PELNs offer broad prospects for future applications, including new drug research and development along with drug carrier selection within targeted drug delivery approaches for cancer therapy.

Industrial-produced lemon nanovesicles ameliorate experimental colitis-associated damages in rats via the activation of anti-inflammatory and antioxidant responses and microbiota modification

Plant-derived nanovesicles (PDNVs) have recently emerged as natural delivery systems of biofunctional compounds toward mammalian cells. Considering their already described composition, anti-inflammatory properties, stability, and low toxicity, PDNVs offer a promising path for developing new preventive strategies for several inflammatory diseases, among which the inflammatory bowel disease (IBD). In this study, we explore the protective effects of industrially produced lemon vesicles (iLNVs) in a rat model of IBD. Characterization of iLNVs reveals the presence of small particles less than 200 nm in size and a profile of bioactive compounds enriched in flavonoids and organic acids with known beneficial properties. In vitro studies on human macrophages confirm the safety and anti-inflammatory effects of iLNVs, as evidenced by the reduced expression of pro-inflammatory cytokines and increased levels of anti-inflammatory markers. As evidenced by in vivo experiments, pre-treatment with iLNVs significantly alleviates symptoms and histological features in 2,4 dinitrobenzensulfuric acid (DNBS)-induced colitis in rats. Molecular pathway analysis reveals modulation of NF-κB and Nrf2, indicating anti-inflammatory and antioxidant effects. Finally, iLNVs affects gut microbiota composition, improving the consistent colitis-related alterations. Overall, we demonstrated the protective role of industrially produced lemon nanovesicles against colitis and emphasized their potential in managing IBD through multifaceted mechanisms.

A randomized double-blind trial to measure the absorption characteristics of eicosapentaenoic acid and docosahexaenoic acid rich oil blend with natural lipid-based delivery system.

A randomized, double-blinded trial with 65 subjects was conducted to compare the pharmacokinetics between PhytoMarineCelle (PM) that consists of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) plus a self-emulsifying drug delivery system (SEDDS), and a standard EPA + DHA ethyl ester (SEE) that does not contain SEDDS. PM showed 1.6-fold greater plasma area under the curve (AUC) than SEE at 300 mg, although no significant difference was observed. PM showed a 3.1 and 3.2-fold (p < 0.05) greater plasma AUC than SEE at 500 mg and 1000 mg respectively. The concentration max (Cmax) of EPA + DHA did not change between PM and SEE at 300 mg. Cmax of PM was twofold greater than SEE at 500 mg and 1000 mg respectively. The Cmax of EPA + DHA achieved significant difference (p < 0.05) only with the 500 mg dose. The PM formulation increased the bioavailability of EPA + DHA by threefold compared to SEE at 500 and 1000 mg.

NANOENCAPSULATION OF LUTEOLIN: ENHANCING BIOAVAILABILITY AND MEDICINAL BENEFITS

Luteolin is a naturally occurring chemical widely found in plants ranging from Bryophyta to Magnoliophyta. It can be obtained from several dietary sources such as carrots, olive oil, celery, spinach, oregano, and, fossils of some organisms such as Celtis and Ulmus dating back 36 to 25 million years. It is synthesized by the Shikimate pathway. The major qualities and therapeutic benefits of luteolin include cytoprotective abilities, Antioxidant, Anti-inflammatory, Anticancer, Antidepressant, Antidiabetic, Antiallergic, Reactive Oxygen Species Scavenging and High radical scavenging. The antioxidant and Reactive Oxygen Species scavenging activity of luteolin aids in treating and curing inflammatory skin processes. It has been proven to act as a therapeutic drug with a wide spectrum of scope in the prevention and treatment of a vast range of malignant and benign cancers, extending from bladder cancer to breast cancer and from oral cancer to glioblastoma, which is achieved by its anticancer, antioxidant properties and cytoprotective abilities. Apart from its anticancer properties, it has a great scope in the restoration from neuropsychiatric disease and high-level fatigue due to Long COVID syndrome-associated brain fog and Chemo fog. The poor solubility and low bioavailability of luteolin limit its use in food and medicine. Synthetic and Natural polymer-based delivery systems have been developed to improve its stability and bioavailability. This review will highlight recent research on its nanoencapsulation and provide more information on luteolin to help readers have a better grasp of the compound's medicinal benefits.

Bio-clickable, small extracellular vesicles-COCKTAIL therapy for ischemic stroke

Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe and targeted delivery to the brain requires an efficient, natural, and non-immunogenic delivery technique. Small extracellular vesicles (sEVs) have shown great potential as a non-immunogenic, natural cargo delivery system; however, tailoring of its inefficient brain targeting is desired. Here, we coupled rabies virus glycoprotein 29 with sEVs surface via bio-orthogonal click chemistry reactions, followed by loading of NR2B9c, ultimately generating stroke-specific therapeutic COCKTAIL (sEVs-COCKTAIL). Primary neurons and Neuro-2a cells were cultured for in vitro and transient middle cerebral artery occlusion model was used for in vivo studies to evaluate neuron targeting and anti-ischemic stroke potential of the sEVs-COCKTAIL. Bio-clickable sEVs were selectively taken up by neurons but not glial cells. In the in vitro ischemic stroke model of oxygen-glucose deprivation, the sEVs-COCKTAIL exhibited remarkable potential against reactive oxygen species and cellular apoptosis. In vivo studies further demonstrated the brain targeting and increased half-life of bio-clickable sEVs, delivering NR2B9c to the ischemic brain and reducing stroke injury. Treatment with the sEVs-COCKTAIL significantly increased behavioral recovery and reduced neuronal apoptosis after transient middle cerebral artery occlusion. NR2B9c was delivered to neurons binding to post-synaptic density protein-95, inhibiting N-methyl-d-Aspartate receptor-mediated over production of oxidative stress and mitigating protein B-cell lymphoma 2 and P38 proteins expression. Our results provide an efficient and biocompatible approach to a targeted delivery system, which is a promising modality for stroke therapy.

Side-chain alanine-based block copolymer as natural product delivery system

To prepare alanine containing amphiphilic block copolymers, herein, we have polymerized methyl methacrylate (MMA) by reversible addition-fragmentation chain transfer (RAFT) polymerization and further used it as macro chain transfer agent (macroCTA) for the synthesis of PMMA-b-P(Boc-L-Ala-HEMA) (Boc-L-Ala-HEMA = tert-butyloxycarbonyl-L-alanine methacryloyloxyethyl ester) diblock copolymers. The molar masses of the macroCTA and all block copolymers as well as the dispersity (Ð) of those polymers were measured by size exclusion chromatography (SEC). The Boc-group deprotection from the block copolymers was carried out in dichloromethane by using trifluoroacetic acid to produce amphiphilic PMMA-b-P(L-Ala-HEMA), and this successful deprotection was proved by 1H NMR spectroscopy. The micellar self-assembled nature of PMMA-b-P(L-Ala-HEMA) was confirmed using a variety of techniques, including dynamic light scattering (DLS), critical aggregation concentration (CAC) determination by fluorescence spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and 1H NMR spectroscopy. The hydrophobic pyrene-tagged estrone-based natural product (NP) was encapsulated in the micellar nanostructure, proven by fluorescence spectroscopy. This encapsulating power of the corresponding polymers makes them attractive candidates as drug delivery vehicles of natural products, as well as encapsulation and delivery of other hydrophobic drug/dye molecules.

Ultrasound-Responsive Oxygen-Carrying Pollen for Enhancing Chemo-Sonodynamic Therapy of Breast Cancer.

The tumor-suppressing efficacy of either chemotherapeutics or gaseous drugs has been confirmed in treating the triple negative breast cancer (TNBC), while the efficacy of single treatment is usually dissatisfactory. Herein, a novel ultrasound responsive natural pollen delivery system is presented to simultaneously load chemotherapeutics and gaseous drugs for synergistic treatment of TNBC. The hollow structure of pollen grains carries oxygen-enriched perfluorocarbon (PFC), and the porous spinous process structure adsorbs the chemotherapeutic drug doxorubicin (DOX) (PO/D-PGs). Ultrasound can trigger the oxygen release from PFC and excite DOX, which is not only a chemotherapeutic but also a sonosensitizer, to realize chemo-sonodynamic therapy. The PO/D-PGs are demonstrated to effectively enhance oxygen concentration and increase the production of reactive oxygen species in the presence of low-intensity ultrasound, synergistically enhancing the tumor killing ability. Thus, the synergistic therapy based on ultrasound-facilitated PO/D-PGs significantly enhances the antitumor effect in the mouse TNBC model. It is believed that the proposed natural pollen cross-state microcarrier can be used as an effective strategy to enhance chemo-sonodynamic therapy for TNBC.

Antioxidant, Antibacterial and Antibiofilm Activity of Nanoemulsion-Based Natural Compound Delivery Systems Compared with Non-Nanoemulsified Versions.

This study aimed to develop nanoemulsions with a focus on improving the bioactivity of oregano essential oil (OEO), carvacrol and thymol for possible food applications. Nanoemulsions were prepared with acoustic cavitation using ultrasound. The nanodroplets had average diameters of 54.47, 81.66 and 84.07 nm for OEO, thymol and carvacrol, respectively. The main compound in OEO was carvacrol (74%), and the concentration in the nanoemulsions was 9.46 mg/mL for OEO and the isolated compounds. The effects of droplet size reduction on antioxidant, antibacterial and antibiofilm activity were evaluated. Regarding antioxidant activity, the nanoemulsions performed better at the same concentration, with inhibitions >45% of the DPPH radical and significant differences compared with their non-nanoemulsified versions (p < 0.05). The nanoemulsions' minimum inhibitory concentration (MIC) and non-nanoemulsified compounds were evaluated against foodborne pathogens with inhibition ranges between 0.147 and 2.36 mg/mL. All evaluated pathogens were more sensitive to nanoemulsions, with reductions of up to four times in MIC compared with non-nanoemulsified versions. E. coli and S. Enteritidis were the most sensitive bacteria to the carvacrol nanoemulsion with MICs of 0.147 mg/mL. Concerning antibiofilm activity, nanoemulsions at concentrations up to four times lower than non-nanoemulsified versions showed inhibition of bacterial adhesion >67.2% and removal of adhered cells >57.7%. Overall, the observed effects indicate that droplet size reduction improved the bioactivity of OEO, carvacrol and thymol, suggesting that nanoemulsion-based delivery systems for natural compounds may be alternatives for food applications compared with free natural compounds.

Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy.

Gene editing-based therapeutic strategies grant the power to override cell machinery and alter faulty genes contributing to disease development like cancer. Nowadays, the principal tool for gene editing is the clustered regularly interspaced short palindromic repeats-associated nuclease 9 (CRISPR/Cas9) system. In order to bring this gene-editing system from the bench to the bedside, a significant hurdle remains, and that is the delivery of CRISPR/Cas to various target cells in vivo and in vitro. The CRISPR-Cas system can be delivered into mammalian cells using various strategies; among all, we have reviewed recent research around two natural gene delivery systems that have been proven to be compatible with human cells. Herein, we have discussed the advantages and limitations of viral vectors, and extracellular vesicles (EVs) in delivering the CRISPR/Cas system for cancer therapy purposes.

Research Progress of Extracellular Vesicles Targeted Therapy

AbstractExtracellular vesicles (EVs), including exosomes, have inherent homing ability in damage repair and drug delivery. However, they have poor targeting and low enrichment efficiency and are easily internalized/cleared by monocyte phagocyte system. If the targeting ability of exosomes can be improved through a series of means, better use can be made of the advantages of exosome therapy and drug delivery. It is necessary to ensure a certain retention rate to study signal pathways and potential mechanisms, especially in flowing blood. This article mainly reviews the research progress of specific targeting based on exosomes, including intrinsic targeting, enhanced targeting, and drug delivery. Inherent targeting is mainly analyzed from different cell sources, and enhanced targeting is mainly from ligand modification and the application of nano materials to improve the targeting ability. To be successfully applied in clinical practice, many problems and challenges still need to be faced in exosome therapy. Herein, the latest knowledge of using EVs as a natural delivery system for disease treatment is summarized.

Modulating Inflammation-Mediated Diseases via Natural Phenolic Compounds Loaded in Nanocarrier Systems.

The global increase and prevalence of inflammatory-mediated diseases have been a great menace to human welfare. Several works have demonstrated the anti-inflammatory potentials of natural polyphenolic compounds, including flavonoid derivatives (EGCG, rutin, apigenin, naringenin) and phenolic acids (GA, CA, etc.), among others (resveratrol, curcumin, etc.). In order to improve the stability and bioavailability of these natural polyphenolic compounds, their recent loading applications in both organic (liposomes, micelles, dendrimers, etc.) and inorganic (mesoporous silica, heavy metals, etc.) nanocarrier technologies are being employed. A great number of studies have highlighted that, apart from improving their stability and bioavailability, nanocarrier systems also enhance their target delivery, while reducing drug toxicity and adverse effects. This review article, therefore, covers the recent advances in the drug delivery of anti-inflammatory agents loaded with natural polyphenolics by the application of both organic and inorganic nanocarriers. Even though nanocarrier technology offers a variety of possible anti-inflammatory advantages to naturally occurring polyphenols, the complexes' inherent properties and mechanisms of action have not yet been fully investigated. Thus, expanding the quest on novel natural polyphenolic-loaded delivery systems, together with the optimization of complexes' activity toward inflammation, will be a new direction of future efforts.

Improving shikonin solubility and stability by encapsulation in natural surfactant‐coated shikonin nanoparticles

It is significant to develop a colloidal delivery system to improve the water solubility, stability, and bioavailability of shikonin, which is a hydrophobic plant polyphenol with a variety of physiological activities. In this study, three kinds of natural surfactants (saponin, sophorolipid, and rhamnolipid) were used to prepare shikonin nanoparticles by the pH-driven method. The physicochemical and structural properties of the shikonin nanoparticles were characterized, including particle size, zeta potential, and morphology. The encapsulation efficiencies of shikonin nanoparticles coated with saponin and sophorolipid were 97.6% and 97.3%, respectively, which were much higher than that of rhamnolipid-coated shikonin nanoparticles (19.0%). Shikonin nanoparticles coated with saponin and sophorolipid showed good resistance to heat and light and maintained long-term stability during storage. Moreover, shikonin nanoparticles coated with saponin and sophorolipid improved their in vitro-bioavailability. PRACTICAL APPLICATION: These article results are of great importance for improving the stability and bioavailability of shikonin in functional foods, dietary supplements, or pharmaceutical preparations. Moreover, this study provided theoretical and practical guides for further research of shikonin nanoparticles and may promote the development of natural colloidal delivery systems.

Construction of curcumin-fortified juices using their self-derived extracellular vesicles as natural delivery systems: grape, tomato, and orange juices.

Different fruit and vegetable juices were first used to encapsulate curcumin to improve its solubility, stability, and bioaccessibility, which is expected to enable designing of polyphenol-enriched beverages and impact human health and well-being. Briefly, fruit and vegetable-derived extracellular vesicles usually serve as transport and communication tools between different cells, which means they also may be utilized as delivery carriers for other bioactive agents. Curcumin, as a model polyphenol with many physiological activities, typically has low water-solubility, stability, and bioaccessibility. Therefore, extracellular vesicles were applied to load curcumin to overcome these challenges and to facilitate its incorporation into fruit and vegetable juices. Three kinds of curcumin-loaded fruit and vegetable juices, including curcumin-loaded grape (Cur-G), tomato (Cur-T), and orange (Cur-O) juices, exhibited higher encapsulation efficiency (>80%) than others. The patterns of XRD and FTIR confirmed that curcumin moved into extracellular vesicles in the amorphous form and that the hydrogen bonding force was found between them. Three kinds of fruit and vegetable juices can significantly enhance the solubility, stability and bioavailability of curcumin, but the degrees of improvement are different. For instance, Cur-O exhibited the highest encapsulation efficiency, chemical stability, and effective bioaccessibility than Cur-G and Cur-T. In summary, this study shows that natural fruit and vegetable juices can effectively improve the solubility, stability and bioaccessibility of active polyphenols, which is expected to enable successful designing of nutrient-enriched beverages with a simple method according to various needs of people and be directly applied to food processing and home production.

Application of exosomes as nanocarriers in cancer therapy.

Cancer remains the most common lethal disease in the world. Although the treatment choices for cancer are still limited, significant progress has been made over the past few years. By improving targeted drug therapy, drug delivery systems promoted the therapeutic effects of anti-cancer medications. Exosome is a kind of natural nanoscale delivery system with natural substance transport properties, good biocompatibility, and high tumor targeting, which shows great potential in drug carriers, thereby providing novel strategies for cancer therapy. In this review, we present the formation, distribution, and characteristics of exosomes. Besides, extraction and isolation techniques are discussed. We focus on the recent progress and application of exosomes in cancer therapy in four aspects: exosome-mediated gene therapy, chemotherapy, photothermal therapy, and combination therapy. The current challenges and future developments of exosome-mediated cancer therapy are also discussed. Finally, the latest advances in the application of exosomes as drug delivery carriers in cancer therapy are summarized, which provide practical value and guidance for the development of cancer therapy.

Exosomes derived from lung cancer cells: Isolation, characterization, and stability studies

Recent advances in nanomedicine have paved the way for developing targeted drug delivery systems. Nanoscale exosomes are present in almost every body fluid and represent a novel mechanism of intercellular communication. Because of their membrane origin, they easily fuse with cells, acting as a natural delivery system and maintaining the bioactivity and immunotolerance of cells. To develop a reconstitutable exosome-based drug candidate for clinical applications, quality assurance by preserving its physical and biological properties during storage is necessary. Therefore, this study aimed to determine the best storage conditions for exosomes derived from lung cancer cells (A549). This study established that the phosphate-buffered saline buffer enriched with 25 mM trehalose is an optimal cryoprotectant for A549-derived exosomes stored at −80°C. Under these conditions, the concentration, size distribution, zeta potential, and total cargo protein levels of the preserved exosomes remained constant.

The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System.

Drug delivery system (DDS) realizes the drug delivery process through the drug carrier. As an important part of DDS, the selection of the drug carrier material is extremely critical, which requires the carrier material to possess excellent biocompatibility and targeting and not affect the pharmacological action of the drug. As one of the endogenous extracellular vesicles, exosomes are 30-100 nm in diameter, which are considered a new generation of a natural nanoscale delivery system. Exosomes secreted by different types of cells carry signaling molecules (such as proteins and nucleic acid) playing an important role in cell behaviors. Owing to their ability to specialize in intercellular communication, exosomes provide a distinctive method to deliver therapeutic drugs to target cells. In this concept, exosomes as the natural liposomes carry endogenous biomolecules, have excellent biocompatibility, and could be loaded with cargo both in vivo and in vitro. In addition, modifications by genetic and/or chemical engineering to part of the exosome surface or complement the desired natural effect may enhance the targeting with drug loading capability. Notably, exosomes weakly react with serum proteins prolonging cargo half-life. Overall, exosomes as natural carriers integrate the superiority of synthetic nanocarriers and cellular communication while precluding their limitations, which provides novel and reliable methods for drug delivery and treatment. Our review focuses on the therapeutic potentials and clinical values of exosomes as a carrier of drug delivery system in multiple diseases, including cancer, nervous, immune, and skeletal system diseases.