scholarly journals EV Cargo Sorting in Therapeutic Development for Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1500
Author(s):  
Cherrie D. Sherman ◽  
Shweta Lodha ◽  
Susmita Sahoo

Cardiovascular disease remains the leading cause of morbidity and mortality in the world. Thus, therapeutic interventions to circumvent this growing burden are of utmost importance. Extracellular vesicles (EVs) actively secreted by most living cells, play a key role in paracrine and endocrine intercellular communication via exchange of biological molecules. As the content of secreted EVs reflect the physiology and pathology of the cell of their origin, EVs play a significant role in cellular homeostasis, disease pathogenesis and diagnostics. Moreover, EVs are gaining popularity in clinics as therapeutic and drug delivery vehicles, transferring bioactive molecules such as proteins, genes, miRNAs and other therapeutic agents to target cells to treat diseases and deter disease progression. Despite our limited but growing knowledge of EV biology, it is imperative to understand the complex mechanisms of EV cargo sorting in pursuit of designing next generation EV-based therapeutic delivery systems. In this review, we highlight the mechanisms of EV cargo sorting and methods of EV bioengineering and discuss engineered EVs as a potential therapeutic delivery system to treat cardiovascular disease.

2021 ◽  
Author(s):  
Moataz Dowaidar

The delivery of therapeutic drugs to the heart continues to be a challenge. Developing precise strategies to target the heart is equally as important as discovering new therapeutic medications. To grow this sector, a program that focuses on targeted delivery to the heart, as well as efforts to improve cardiac selectivity and retention of therapeutic medications, may be required. Targeted medicine distribution is one of the most important and unresolved issues in pharmacology. Viruses, on the other hand, have evolved unique and extremely accurate tropisms toward their biological targets through the usage of specific binding proteins. The inclusion of these viral proteins into the plasma membrane of EVs should improve the efficiency with which EVs transport drugs to target cells. Understanding the structure, content, and mechanisms of exosome–cell interactions and uptake might also help with the creation of bioengineered exosomes and other EVs that might be used as targeted drug delivery vehicles. In addition to establishing the optimal vector for each therapeutic ingredient, effective clinical translation of cardiac medicines requires minimally invasive yet highly selective delivery techniques.


1995 ◽  
Vol 394 ◽  
Author(s):  
Nir Kossovsky

AbstractThe structural denaturation of polypeptides and other macromolecular pharmaceuticals upon surface adsorption from an aqueous environment is almost inevitable. Molecular denaturation, coupled with a net increase in entropy, accounts for the net negative ΔG and frequent irreversible nature of surface adsorption. The consequence of this interaction is that surface immobilized drugs lose their dynamic freedom and thus, all too often, their biological activity.This phenomenon has complicated the development of drug delivery vehicles. In this communication, a drug delivery system based on a novel surface modification process to help reverse the constraining activity of surfaces is described. Beginning with preformed carbon ceramic nanoparticles and self-assembled calcium-phosphate dihydrate particles (colloidal precipitation) to which glassy carbohydrates are then allowed to adsorb as a nanometer thick surface coating, a molecular carrier is formed. The carbohydrate coating functions as a dehydroprotectant and stabilizes subsequently non-covalently bound immobilized members of biochemically reactive surface members such as pharmaceuticals.Many of the physical properties of this enabling system have been characterized in vitro and in animal models. Antigen delivery, drug delivery, and enzyme stabilization experiments are described.


2020 ◽  
Vol 22 (1) ◽  
pp. 14
Author(s):  
Hyosuk Kim ◽  
Eun Hye Kim ◽  
Gijung Kwak ◽  
Sung-Gil Chi ◽  
Sun Hwa Kim ◽  
...  

Exosomes are cell-secreted nanovesicles that naturally contain biomolecular cargoes such as lipids, proteins, and nucleic acids. Exosomes mediate intercellular communication, enabling the transfer biological signals from the donor cells to the recipient cells. Recently, exosomes are emerging as promising drug delivery vehicles due to their strong stability in blood circulation, high biocompatibility, low immunogenicity, and natural targeting ability. In particular, exosomes derived from specific types of cells can carry endogenous signaling molecules with therapeutic potential for cancer treatment, thus presenting a significant impact on targeted drug delivery and therapy. Furthermore, exosomes can be engineered to display targeting moieties on their surface or to load additional therapeutic agents. Therefore, a comprehensive understanding of exosome biogenesis and the development of efficient exosome engineering techniques will provide new avenues to establish convincing clinical therapeutic strategies based on exosomes. This review focuses on the therapeutic applications of exosomes derived from various cells and the exosome engineering technologies that enable the accurate delivery of various types of cargoes to target cells for cancer therapy.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 564 ◽  
Author(s):  
Saber H. Saber ◽  
Hamdy E. A. Ali ◽  
Rofaida Gaballa ◽  
Mohamed Gaballah ◽  
Hamed I. Ali ◽  
...  

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.


2020 ◽  
Vol 21 (24) ◽  
pp. 9598
Author(s):  
Alina Constantin ◽  
Alexandru Filippi ◽  
Nicoleta Alexandru ◽  
Miruna Nemecz ◽  
Adriana Georgescu

Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. “Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication between cells, transferring their specific bioactive molecules into host target cells”. There is a general consensus on how to define and isolate ADSCs, however, multiple separation and characterization protocols are being used in the present which complicate the results’ integration in a single theory on ADSCs’ and their derived factors’ way of action. Metabolic syndrome and type 2 diabetes mellitus (T2DM) are mainly caused by abnormal adipose tissue size, distribution and metabolism and so ADSCs and their secretory factors such as EVs are currently investigated as therapeutics in these diseases. Moreover, due to their relatively easy isolation and propagation in culture and their differentiation ability, ADSCs are being employed in preclinical studies of implantable devices or prosthetics. This review aims to provide a comprehensive summary of the current knowledge on EVs secreted from ADSCs both as diagnostic biomarkers and therapeutics in diabetes and associated cardiovascular disease, the molecular mechanisms involved, as well as on the use of ADSC differentiation potential in cardiovascular tissue repair and prostheses.


Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 3
Author(s):  
Ana Ortega ◽  
Olga Martinez-Arroyo ◽  
Maria J. Forner ◽  
Raquel Cortes

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.


2018 ◽  
Vol 25 (25) ◽  
pp. 2987-3000 ◽  
Author(s):  
Linying Liu ◽  
Xiaoshuang Li ◽  
Lei Chen ◽  
Xin Zhang

Nanomedicine is widely developed in recent years. In nanomedicine system, nanoscale and nanostructured functional materials are used to manipulate the human biology systems at the molecular level for cancer imaging and therapy. New nanostructure based functional materials consist of nanoscale liposomes, spheres, micelles, capsules, emulsion, suspension and phamacosomes. Several functional nanoparticles such as lipidbased and polymer-based materials are demonstrated to be drug delivery vehicles and imaging agents. These materials are biodegradable, biocompatible and have better biodistribution, lower side effect and lower toxicity. In addition, hybrids with these materials coating provide uniquely electrical, optical and magnetic properties. This review discusses the research on the applications of functional materials, especially nanoparticles as imaging contrast agents, cancer therapeutic agents and multi-functional agents and this review focused on the theranostic integration treatments on liver cancer and brain cancer.


2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.


2020 ◽  
Vol 17 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Xueying Zhou ◽  
Zhelong Li ◽  
Wenqi Sun ◽  
Guodong Yang ◽  
Changyang Xing ◽  
...  

Background: Exosomes are cell-derived nanovesicles that play vital roles in intercellular communication. Recently, exosomes are recognized as promising drug delivery vehicles. Up till now, how the in vivo distribution of exosomes is affected by different administration routes has not been fully understood. Methods: In the present study, in vivo distribution of exosomes following intravenous and intraperitoneal injection approaches was systemically analyzed by tracking the fluorescence-labeled exosomes and qPCR analysis of C. elegans specific miRNA abundance delivered by exosomes in different organs. Results: The results showed that exosomes administered through tail vein were mostly taken up by the liver, spleen and lungs while exosomes injected intraperitoneally were more dispersedly distributed. Besides the liver, spleen, and lungs, intraperitoneal injection effectively delivered exosomes into the visceral adipose tissue, making it a promising strategy for obesity therapy. Moreover, the results from fluorescence tracking and qPCR were slightly different, which could be explained by systemic errors. Conclusion: Together, our study reveals that different administration routes cause a significant differential in vivo distribution of exosomes, suggesting that optimization of the delivery route is prerequisite to obtain rational delivery efficiency in detailed organs.


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