Therapeutic Drug Delivery Research Articles

Impact of the functional coating of silver nanoparticles on their in vivo performance and biosafety

Objective and significance Silver nanoparticles (AgNPs) have become an interesting therapeutic modality and drug delivery platform. Herein, we aimed to investigate the impact of functional coating on the in vivo performance of AgNPs as an economic and scalable method to modulate their behavior. Methods AgNPs were coated with chitosan (CHI) as a model biopolymer using a one-pot reduction-based method, where CHI of two molecular weight ranges were investigated. The resultant CHI-coated AgNPs (AgNPs-CHI) were characterized using UV-VIS spectroscopy, DLS, and TEM. AgNPs were administered intravenously to rats and their biodistribution and serum levels of hepato-renal function markers were monitored 24 h later compared to plain AgNO3 as a positive control. Results UV-VIS spectroscopy confirmed the successful coating of AgNPs with CHI. DLS revealed the superiority of medium molecular weight CHI over its low molecular weight counterpart. AgNPs-CHI demonstrated a semi-complete clearance from the systemic circulation, a liver-dominated tissue tropism, and limited renal exposure. On the other hand, AgNO3 was poorly cleared from the circulation, with relatively high renal exposure and a non-specific tissue tropism. AgNPs-CHI were well-tolerated by the liver and kidney without signs of toxicity or inflammation, in contrary with AgNO3 which resulted in a significant elevation of Creatinine (CRE), Urea, and Total Protein (TP), suggesting a significant nephrotoxicity and inflammation. Conclusions Functional coating of AgNPs with CHI substantially modulated their in vivo behavior, promoting their hepatic selectivity and biotolerability, which can be invested in the development of drug delivery systems for the treatment of liver diseases.

An Overview of Dendrimers as Novel Carriers in Drug Delivery

Dendrimers and dendrimer based nanocarriers are gaining much attention in the field of therapeutic drug delivery owing to their advantages such as ease of multifunctionalization, well-defined chemical structure, near-to-monodispersity, as well as multivalency. Dendrimers are used as vectors in gene therapy, solubility enhancers and blood substitutes. Dendrimers have also been investigated as genetic material carriers with potential diagnostic and therapeutic applications. In the current review, an overview of the different types, synthesis methods, unique structural properties, factors affecting properties and applications of dendrimers. Further, the major concerns and future perspectives of the dendrimers have been discussed. The surface-modified dendrimers have been succeeded in their clinical translation and making remarkable progress in the phase of clinical trials. Extensive research is required in order to foster a robust large-scale synthetic method with adequate reproducibility. Significant studies necessarily be carriedout to find the correlation between the degree of surface modification (product quality) and their biological behavior, like pharmacokinetic profiles, therapeutic efficiency, safety and toxicity. In conclusion, dendrimers and dendritic nanoparticles have prospective insight in the arena of health sector in the forthcoming years.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

Dual Targeted Delivery of Liposomal Hybrid Gold Nano-Assembly for Enhanced Photothermal Therapy against Lung Carcinomas

The delivery and accumulation of therapeutic drugs into cancer cells without affecting healthy cells are a major challenge for antitumor therapy. Here, we report the synthesis of a liposomal hybrid gold nano-assembly with enhanced photothermal activity for lung cancer treatment. The core components of the nano-assembly include gold nanorods coated with a mesoporous silica shell that offers an excellent drug-loading surface for encapsulation of doxorubicin. To enhance the photothermal capacity of nano-assembly, IR 780 dye was loaded inside a thermo-sensitive liposome, and then, the core nano-assembly was wrapped within the liposome, and GE-11 peptide and folic acid were conjugated onto the surface of the liposome to give the final nano-assembly [(GM@Dox) LI]-PF. The dual targeting approach of [(GM@Dox) LI]-PF leads to enhanced cellular uptake and improves the accumulation of nano-assemblies in cancer cells that overexpress the epidermal growth factor receptor and folate. The exposure of near-infrared laser irradiation can trigger photothermal-induced structural disruption of the nano-assembly, which allows for the precise and controllable release of Dox at targeted sites. Additionally, chemo-photothermal therapy was shown to be 11 times more effective in cancer cell treatment when compared to Dox alone. Our systematic study suggests that the nano-assemblies facilitate the cancer cells undergoing apoptosis via an intrinsic mitochondrial pathway that can be directly triggered by the chemo-photothermal treatment. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.

A folic acid-decorated nanoparticles loaded JQ1 for oral squamous cell carcinoma therapy

Oral squamous cell carcinoma (OSCC) is known as one of the most malignant tumors with high recurrence and fatality rate. The poor tumor-targeting ability of traditional chemotherapeutic drugs has been a grand challenge for anti-OSCC therapy. Beyond that, a large quantity of tumor associated macrophages in OSCC tissues further diminish the anti-tumor effects of these drugs. Therefore, we produced a therapeutic nano drug delivery system (FA-PEG-PLA-JQ1) through encapsulating JQ1 [a small-molecule inhibitor of bromodomain containing protein 4 (BRD4)] into the folic acid (FA)-modified nanoparticle (PEG-PLA), which could prolong the half-life of JQ1 and target the tumor tissues. And then, JQ1 released from this nanoparticle could prevent OSCC growth inducing tumor cell apoptosis, inhibiting tumor angiogenesis and the polarization of M2 type macrophages. In conclusion, our date demonstrated the therapeutic benefits of FA-PEG-PLA-JQ1 against OSCC in vivo or in vitro, which could be a novel treatment strategy for OSCC in coming days.

Enhanced and Extended Ophthalmic Drug Delivery by pH-Triggered Drug-Eluting Contact Lenses with Large-Pore Mesoporous Silica Nanoparticles

Drug-eluting contact lenses (DCLs) have attracted considerable attention as potential therapeutic ophthalmic drug delivery devices. In this study, we propose, fabricate, and investigate pH-triggered DCLs that are combined with large-pore mesoporous silica nanoparticles (LPMSNs). Compared to reference DCLs, LPMSN-laden DCLs can prolong the residence time of glaucoma drugs in an artificial lacrimal fluid (ALF) environment at pH 7.4. Additionally, LPMSN-laden DCLs do not require drug preloading and are compatible with current contact lens manufacturing processes. LPMSN-laden DCLs soaked at pH 6.5 exhibit better drug loading than reference DCLs due to their specific adsorption. The sustained and extended release of glaucoma drugs by LPMSN-laden DCLs was successfully monitored in ALF, and the drug release mechanism was further explained. We also evaluated the cytotoxicity of LPMSN-laden DCLs, and qualitative and quantitative results showed no cytotoxicity. Our experimental results demonstrate that LPMSNs are excellent nanocarriers that have the potential to be used as safe and stable nanocarriers for the delivery of glaucoma drugs or other drugs. pH-triggered LPMSN-laden DCLs can significantly improve drug loading efficiency and control prolonged drug release, indicating that they have great potential for future biomedical applications.

Nanotechnology-enabled gene delivery for cancer and other genetic diseases

Introduction Despite gene therapy is ideal for genetic abnormality-related diseases, the easy degradation, poor targeting, and inefficiency in entering targeted cells are plaguing the effective delivery of gene therapy. Viral and non-viral vectors have been used for delivering gene therapeutics in vivo by safeguarding nucleic acid agents to target cells and to reach the specific intracellular location. A variety of nanotechnology-enabled safe and efficient systems have been successfully developed to improve the targeting ability for effective therapeutic delivery of genetic drugs. Areas covered In this review, we outline the multiple biological barriers associated with gene delivery process, and highlight recent advances to gene therapy strategy in vivo, including gene correction, gene silencing, gene activation and genome editing. We point out current developments and challenges exist of non-viral and viral vector systems in association with chemical and physical gene delivery technologies and their potential for the future. Expert opinion This review focuses on the opportunities and challenges to various gene therapy strategy, with specific emphasis on overcoming the challenges through the development of biocompatibility and smart gene vectors for potential clinical application.

Recent Progress in Advanced Hydrogel-Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization.

Transcatheter arterial embolization, a minimally invasive treatment to deliberately occlude the blood vessels, has become a safe and effective procedure for the management of vascular diseases and benign/malignant tumors. Particularly, hydrogel-based embolic agents have garnered much attention because of their potential to address some of the limitations of clinically used embolic agents and can be rationally designed to impart more favorable characteristics or functions. In this review, the recent progress toward the development of polymer-based hydrogels for effective endovascular embolization, including the in situ gelling hydrogels mediated by physically or chemically crosslinking, imageable hydrogels for intraprocedural and postprocedural feedback, use of hydrogels as the drug depot for local delivery of therapeutic drugs, hemostatic hydrogels inducing extrinsic or intrinsic coagulation of blood, stimuli-responsive shape memory hydrogels as the smart embolization devices, and hydrogels incorporating external-stimuli functional materials for multidisciplinary therapy, is systemically summarized. Moreover, the potential considerations of hydrogel-based embolic agents confronted in therapeutic embolization are pointed out. Finally, the perspectives for the development of more effective embolic hydrogels are also highlighted.

Computational estimation of drug’s concentration distribution through a microporous membrane using artificial intelligence approach

Recently, the emergence of promising membrane-based processes in disparate related disciplines of pharmaceutical industries (i.e., biochemical engineering and biotechnology) has paved the way towards concentration and purification of therapeutic entities, molecular synthesis, and drug delivery. The strategy of this investigation is to employ various artificial intelligence (AI)-based computational models as a novel method to estimate the concentration distribution value of a medical solute inside the membrane. To achieve this, a data set with two inputs and one output was analyzed using bagging ensemble method with some distinct base models. The base models are Multi-layer Perceptron (MLP), Linear Regression (LR), and K-Nearest Neighbor (KNN). The hyperparameters of the methods were developed through performing a grid search and the final models were examined. Based on this, as expected, the use of bagging along with the optimization of hyperparameters led to strong models. All three bagging models with the R-square measure have scores higher than 0.98. Also, in terms of RMSE bagging LR, bagging MLP, and bagging KNN have error rates of 9.25 × 101, 2.29 × 101, 9.57 × 101, respectively.

Application of co-processed excipients for developing fast disintegrating tablets: A review.

The introduction of tablet dosage forms has brought a revolution in the pharmaceutical drug delivery system. Different forms of tablets have been developed based on the target site, the onset of action, and therapeutic drug delivery methods. Fast-disintegrating tablets (FDTs) are the most promising pharmaceutical dosage form, especially for pediatric and geriatric patients having difficulty swallowing. The key feature of FDTs is quick drug release soon after their administration through the oral cavity. With innovations in the formulation of FDTs, the demand for excipients with better functionalities, particularly in terms of flow and compression characteristics, has increased. Co-processed excipients are a mixture of 2 or more conventional excipients that provides significant benefits over the individual excipients while minimizing their shortcomings. Such multifunctional co-processed excipients minimize the number of excipients that are to be incorporated into tablets during the manufacturing process. The present review discusses FTDs formulated from co-processed excipients, their manufacturing techniques, and the latest research, patents and commercially available co-processed FDTs.

Simple Complexity: Incorporating Bioinspired Delivery Machinery within Self-Assembled Peptide Biogels.

Bioinspired self-assembly is a bottom-up strategy enabling biologically sophisticated nanostructured biogels that can mimic natural tissue. Self-assembling peptides (SAPs), carefully designed, form signal-rich supramolecular nanostructures that intertwine to form a hydrogel material that can be used for a range of cell and tissue engineering scaffolds. Using the tools of nature, they are a versatile framework for the supply and presentation of important biological factors. Recent developments have shown promise for many applications such as therapeutic gene, drug and cell delivery and yet are stable enough for large-scale tissue engineering. This is due to their excellent programmability-features can be incorporated for innate biocompatibility, biodegradability, synthetic feasibility, biological functionality and responsiveness to external stimuli. SAPs can be used independently or combined with other (macro)molecules to recapitulate surprisingly complex biological functions in a simple framework. It is easy to accomplish localized delivery, since they can be injected and can deliver targeted and sustained effects. In this review, we discuss the categories of SAPs, applications for gene and drug delivery, and their inherent design challenges. We highlight selected applications from the literature and make suggestions to advance the field with SAPs as a simple, yet smart delivery platform for emerging BioMedTech applications.

The role of acoustofluidics and microbubble dynamics for therapeutic applications and drug delivery.

Targeted drug delivery is proposed to reduce the toxic effects of conventional therapeutic methods. For that purpose, nanoparticles are loaded with drugs called nanocarriers and directed toward a specific site. However, biological barriers challenge the nanocarriers to convey the drug to the target site effectively. Different targeting strategies and nanoparticle designs are used to overcome these barriers. Ultrasound is a new, safe, and non-invasive drug targeting method, especially when combined with microbubbles. Microbubbles oscillate under the effect of the ultrasound, which increases the permeability of endothelium, hence, the drug uptake to the target site. Consequently, this new technique reduces the dose of the drug and avoids its side effects. This review aims to describe the biological barriers and the targeting types with the critical features of acoustically driven microbubbles focusing on biomedical applications. The theoretical part covers the historical developments in microbubble models for different conditions: microbubbles in an incompressible and compressible medium and bubbles encapsulated by a shell. The current state and the possible future directions are discussed.

Establishment of ultrasound-responsive SonoBacteriaBot for targeted drug delivery and controlled release.

Bacteria-driven biohybrid microbots have shown great potential in cancer treatment. However, how precisely controlling drug release at the tumor site is still an issue. To overcome the limitation of this system, we proposed the ultrasound-responsive SonoBacteriaBot (DOX-PFP-PLGA@EcM). Doxorubicin (DOX) and perfluoro-n-pentane (PFP) were encapsulated in polylactic acid-glycolic acid (PLGA) to form ultrasound-responsive DOX-PFP-PLGA nanodroplets. Then, DOX-PFP-PLGA@EcM is created by DOX-PFP-PLGA amide-bonded to the surface of E. coli MG1655 (EcM). The DOX-PFP-PLGA@EcM was proved to have the characteristics of high tumor-targeting efficiency, controlled drug release capability, and ultrasound imaging. Based on the acoustic phase change function of nanodroplets, DOX-PFP-PLGA@EcM enhance the signal of US imaging after ultrasound irradiation. Meanwhile, the DOX loaded into DOX-PFP-PLGA@EcM can be released. After being intravenously injected, DOX-PFP-PLGA@EcM can efficiently accumulate in tumors without causing harm to critical organs. In conclusion, the SonoBacteriaBot has significant benefits in real-time monitoring and controlled drug release, which has significant potential applications for therapeutic drug delivery in clinical settings.

Folate receptor-mediated targeted therapy for rheumatoid arthritis by methotrexate-phospholipid complex nano-emulsions

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease. Activated macrophages in arthritic joints play a prominent role in the initiation and persistence of RA. Despite great progress in the clinical treatment of RA, poor response and high discontinuation due to systemic toxicity remain unsolved issues, especially the well-known methotrexate (MTX). Therefore, active targeted delivery of therapeutic drugs to pathogenic cells in arthritic joints is essential to increase in situ activity and decrease systemic toxicity. Here, we developed an MTX-loaded macrophage-targeted nano-emulsion (NE) based on the overexpression of folate receptor (FR) on activated macrophages, the inherent high affinity of FR for folate (FA), as well as the property of MTX and phospholipids to form complexes (MTX@PC). Intravenous injection of DID-labelled MTX@PC-FA NEs into adjuvant-induced arthritis (AIA) mice, in vivo images and flow cytometry results revealed that the NEs were highly targeted to inflamed joints and macrophages, respectively. Therapeutic studies suggested that this strategy was conducive to achieve high efficacy and low toxicity of MTX in the treatment of RA. Our research highlights MTX@PC-FA NEs as a potential treatment option for RA targeting the FR-expressed activated macrophages.

Hollow Nanomaterials in Advanced Drug Delivery Systems: From Single- to Multiple Shells.

Hollow-structured nanomaterials (HSNMs) have attracted increased interest in biomedical fields, owing to their excellent potential as drug delivery systems (DDSs) for clinical applications. Among HSNMs, hollow multi-shelled structures (HoMSs) exhibit properties such as high loading capacity, sequential drug release, and multi-functionalized modification and represent a new class of nanoplatforms for clinical applications. The remarkable properties of HoMS-based DDS can simultaneously satisfy and enhance DDSs for delivering small molecular drugs (e.g., antibiotics, chemotherapy drugs, and imaging agents) and macromolecular drugs (e.g., protein/peptide- and nucleic acid-based drugs). First, the latest research advances in delivering small molecular drugs are summarized and highlight the inherent advantages of HoMS-based DDSs for small molecular drug targeting, combining continuous therapeutic drug delivery and theranostics to optimize the clinical benefit. Meanwhile, the macromolecular drugs DDSs are in the initial development stage and currently offer limited delivery modes. There is a growing need to analyze the deficiency of other HSNMs and integrate the advantages of HSNMs, providing solutions for the safe, stable, and cascade delivery of macromolecular drugs to meet vast treatment requirements. Therefore, the latest advances in HoMS-based DDSs are comprehensively reviewed, mainly focusing on the characteristics, research progress by drug category, and future research prospects.

Enhanced Corrosion Resistance and Local Therapy from Nano-Engineered Titanium Dental Implants

Titanium is the ideal material for fabricating dental implants with favorable biocompatibility and biomechanics. However, the chemical corrosions arising from interaction with the surrounding tissues and fluids in oral cavity can challenge the integrity of Ti implants and leach Ti ions/nanoparticles, thereby causing cytotoxicity. Various nanoscale surface modifications have been performed to augment the chemical and electrochemical stability of Ti-based dental implants, and this review discusses and details these advances. For instance, depositing nanowires/nanoparticles via alkali-heat treatment and plasma spraying results in the fabrication of a nanostructured layer to reduce chemical corrosion. Further, refining the grain size to nanoscale could enhance Ti implants' mechanical and chemical stability by alleviating the internal strain and establishing a uniform TiO2 layer. More recently, electrochemical anodization (EA) has emerged as a promising method to fabricate controlled TiO2 nanostructures on Ti dental implants. These anodized implants enhance Ti implants' corrosion resistance and bioactivity. A particular focus of this review is to highlight critical advances in anodized Ti implants with nanotubes/nanopores for local drug delivery of potent therapeutics to augment osseo- and soft-tissue integration. This review aims to improve the understanding of novel nano-engineered Ti dental implant modifications, focusing on anodized nanostructures to fabricate the next generation of therapeutic and corrosion-resistant dental implants. The review explores the latest developments, clinical translation challenges, and future directions to assist in developing the next generation of dental implants that will survive long-term in the complex corrosive oral microenvironment.

Bibliometric analysis of scientific papers on extracellular vesicles in kidney disease published between 1999 and 2022.

Background: In recent years, there has been an increasing interest in using extracellular vesicles (EVs) as potential therapeutic agents or natural drug delivery systems in kidney-related diseases. However, a detailed and targeted report on the current condition of extracellular vesicle research in kidney-related diseases is lacking. Therefore, this prospective study was designed to investigate the use of bibliometric analysis to comprehensively overview the current state of research and frontier trends on extracellular vesicle research in kidney-related diseases using visualization tools. Methods: The Web of Science Core Collection (WoSCC) database was searched to identify publications related to extracellular vesicle research in kidney-related diseases since 1999. Citespace, Microsoft Excel 2019, VOSviewer software, the R Bibliometrix Package, and an online platform were used to analyze related research trends to stratify the publication data and collaborations. Results: From 1 January 1999 to 26 June 2022, a total of 1,122 EV-related articles and reviews were published, and 6,486 authors from 1,432 institutions in 63 countries or regions investigated the role of extracellular vesicles in kidney-related diseases. We found that the number of articles on extracellular vesicles in kidney-related diseases increased every year. Dozens of publications were from China and the United States. China had the most number of related publications, in which the Southeast University (China) was the most active institution in all EV-related fields. Liu Bi-cheng published the most papers on extracellular vesicles, while Clotilde Théry had the most number of co-citations. Most papers were published by The International Journal of Molecular Sciences, while Kidney International was the most co-cited journal for extracellular vesicles. We found that exosome-related keywords included exosome, exosm, expression, extracellular vesicle, microRNA, microvesicle, and liquid biopsy, while disease- and pathological-related keywords included biomarker, microRNA, apoptosis, mechanism, systemic lupus erythematosus, EGFR, acute kidney injury, and chronic kidney disease. Acute kidney disease (AKI), CKD, SLE, exosome, liquid biopsy, and extracellular vesicle were the hotspot in extracellular vesicle and kidney-related diseases research. Conclusion: The field of extracellular vesicles in kidney-related disease research is rapidly growing, and its domain is likely to expand in the next decade. The findings from this comprehensive analysis of extracellular vesicles in kidney-related disease research could help investigators to set new diagnostic, therapeutic, and prognostic ideas or methods in kidney-related diseases.

Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy

Radiotherapy is an effective therapy in tumour treatment. However, the characteristics of the tumour microenvironment, including hypoxia, low pH, and interstitial fluid pressure bring about radioresistance. To improve the anti-tumour effect of radiotherapy, it has been demonstrated that antiangiogenic therapy can be employed to repair the structural and functional defects of tumour angiogenic vessels, thereby preventing radioresistance or poor therapeutic drug delivery. In this study, we prepared triptolide (TP)-loaded Asn-Gly-Arg (NGR) peptide conjugated mPEG2000-DSPE-targeted liposomes (NGR-PEG-TP-LPs) to induce tumour blood vessel normalisation, to the end of increasing the sensitivity of tumour cells to radiotherapy. Further, to quantify the tumour vessel normalisation window, the structure and functionality of tumour blood vessels post NGR-PEG-TP-LPs treatment were evaluated. Thereafter, the anti-tumour effect of radiotherapy following these treatments was evaluated using HCT116 xenograft-bearing mouse models based on the tumour vessel normalisation period window. The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment

Application of nanotechnology in bladder cancer diagnosis and therapeutic drug delivery.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system, and its high recurrence rate is a great economic burden to patients. Traditional diagnosis and treatment methods have the disadvantages of insufficient targeting, obvious side effects and low sensitivity, which seriously limit the accurate diagnosis and efficient treatment of BC. Due to their small size, easy surface modification, optical properties such as plasmon resonance, and surface enhanced Raman scattering, good electrical conductivity and photothermal conversion properties, nanomaterials have great potential application value in the realization of specific diagnosis and targeted therapy of BC. At present, the application of nanomaterials in the diagnosis and treatment of BC is attracting great attention and achieving rich research results. Therefore, this paper summarizes the recent research on nanomaterials in the diagnosis and treatment of BC, clarifies the existing advantages and disadvantages, and provides theoretical guidance for promoting the accurate diagnosis and efficient treatment of BC.

Extracellular Vesicles in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of death and disability worldwide. Despite recent progress in the diagnosis and treatment of CAD, evidence gaps remain, including pathogenesis, the most efficient diagnostic strategy, prognosis of individual patients, monitoring of therapy, and novel therapeutic strategies. These gaps could all be filled by developing novel, minimally invasive, blood-based biomarkers. Potentially, extracellular vesicles (EVs) could fill such gaps. EVs are lipid membrane particles released from cells into blood and other body fluids. Because the concentration, composition, and functions of EVs change during disease, and because all cell types involved in the development and progression of CAD release EVs, currently available guidelines potentially enable reliable and reproducible measurements of EVs in clinical trials, offering a wide range of opportunities. In this chapter, we provide an overview of the associations reported between EVs and CAD, including (1) the role of EVs in CAD pathogenesis, (2) EVs as biomarkers to diagnose CAD, predict prognosis, and monitor therapy in individual patients, and (3) EVs as new therapeutic targets and/or drug delivery vehicles. In addition, we summarize the challenges encountered in EV isolation and detection, and the lack of standardization, which has hampered real clinical applications of EVs. Since most conclusions are based on animal models and single-center studies, the knowledge and insights into the roles and opportunities of EVs as biomarkers in CAD are still changing, and therefore, the content of this chapter should be seen as a snapshot in time rather than a final and complete compendium of knowledge on EVs in CAD.