A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy

Tian, Yanhua; Li, Suping; Song, Jinsup; Ji, Tianjiao; Zhu, Motao; Anderson, Gregory J.; Wei, Jingyan; Nie, Guangjun

doi:10.1016/j.biomaterials.2013.11.083

Cited by 1,482 publications

(1,232 citation statements)

References 25 publications

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“…Through phage display35 and in vivo biopanning techniques, lots of core ligand fragments or homing peptides targeting specific organs or tissues have been obtained and verified, so that targeting modification of exosomes can be realized. Displaying the tumor penetration peptide iRGD (CRGDKGPDC)36 on the surface of exosomes enabled them to specifically deliver doxorubicin to breast cancer cells expressing αv integrins, leading to inhibition of tumor growth 37. GE11 peptide (YHWYGYTPQNVI) fused to exosomes facilitates exosomes loaded with therapeutic microRNA targeting epidermal growth factor receptor–positive xenograft breast cancer cells 38.…”

Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

283

206

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BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

283

206

View full text Add to dashboard Cite

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“…For instance, EVs expressing the rabies viral glycoprotein (RVG), a central nervous system‐specific peptide, via binding to the acetylcholine receptor have been shown to selectively deliver siRNA to neural cells, whereas EVs without RVG cannot 20. EVs with αv integrin‐specific arginine–glycine–aspartic acid peptides and loaded with doxorubicin selectively inhibited breast cancer progression, whereas unmodified EVs were mostly eliminated without affecting the tumor 47. Modified EVs have also demonstrated potential in specific targeting of oncogenic KRAS for tumor therapy 109.…”

Section: Modular Design Of Surface Proteinsmentioning

confidence: 99%

“…However, completely natural EVs may not be sufficient to provide treatments for all kinds of disease conditions; modified EVs have therefore been developed, indicating the beginning of the era of modularized EVs. A variety of modified EVs, including EVs specifically enriched in mRNA,42 miRNA,12, 43 and small interfering RNA (siRNA),20, 44 EVs with membrane modification,45, 46 and EVs carrying small molecule drugs47 and superparamagnetic iron oxide nanoparticles48 have been developed. As the era of personalized and precision medicine continues to develop, the demands of both the targeting ability toward pathological organization combined with limited damage to normal tissues49 to minimize side effects (precision medicine) and freely assembled agents based on a patient's personalized database50, 51 to maximize therapeutic effects (personalized medicine) will continually increase.…”

Section: Introductionmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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“…These authors showed that the VSV-G protein stimulated MHC I mediated antigen presentation and elicited an antigen-specific CD8 + T cell response [142]. The previously mentioned RVG targeting ligand [119,144,145] and iRGD [133,146] have also been reported to have membrane-destabilizing properties, possibly contributing to enhanced cytoplasmic delivery of the encapsulated cargo.…”

Section: Intracellular Trafficking Of Evsmentioning

confidence: 98%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

159

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy

Cited by 1,482 publications

References 25 publications

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Therapeutic and diagnostic applications of extracellular vesicles

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