PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time

Kooijmans, Sander A.A.; Fliervoet, Lies A. L.; Meel, Roy van der; Fens, Marcel H.A.M.; Heijnen, Harry F. G.; Henegouwen, Paul M.P. van Bergen en; Vader, Pieter; Schiffelers, Raymond M.

doi:10.1016/j.jconrel.2016.01.009

Cited by 448 publications

(384 citation statements)

References 68 publications

Supporting

Mentioning

378

Contrasting

Order By: Relevance

“…For example, Kooijmans et al reported that polyethyleneglycol (PEG) polymer chains could link cell specific peptides to the EVs surface 57. Jang et al reported that EVs derived from UG37 and Raw264.7 cells exhibited high level of tumor-targeting ability.…”

Section: Discussionmentioning

confidence: 99%

Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer

et al. 2017

View full text Add to dashboard Cite

Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells. This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in vitro as confirmed with fluorescent microscopic imaging and flow cytometry. Also, intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice and inhibited tumor growth. Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response. Thus, the RNAi nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells both in vitro and in vivo. Our results suggest that the AS1411-EVs have a great potential as drug delivery vehicles to treat cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Alternatively, a series of approaches aiming at modifying the EVs after secretion, without the need of manipulating the EVs-producing cells, have been recently pursued (Figure 2). For instance, it is possible to link cell-specific peptides to the EVs surface via association with polyethylene glycol (PEG) polymer chains [77]. The resulting PEGylated EVs are coated with the desired ligand, allowing for specific targeting.…”

Section: Targeting Extracellular Vesicles Deliverymentioning

confidence: 99%

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Rocco¹,

Baldari²,

Toietta³

2016

Stem Cells International

120

101

View full text Add to dashboard Cite

Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge about in vivo EVs trafficking upon delivery is required before effective clinical translation. Only a few studies have focused on the biodistribution analysis of exogenously administered MSCs-derived EVs. Nevertheless, current strategies for in vivo tracking in animal models have provided valuable insights on the biodistribution upon systemic delivery of EVs isolated from several cellular sources, indicating in liver, spleen, and lungs the preferential target organs. Different strategies for targeting EVs to specific tissues to enhance their therapeutic efficacy and reduce possible off-target effects have been investigated. Here, in the context of a possible clinical application of MSC-derived EVs for tissue regeneration, we review the existing strategies for in vivo tracking and targeting of EVs isolated from different cellular sources and the studies elucidating the biodistribution of exogenously administered EVs.

show abstract

“…For instance, hydrophilic PEG chains were inserted in the EV lipid bilayer carrying targeting nanobodies at their distal end to both shield the EV surface from off-target interactions (leading to a prolonged circulation time) yet allow specific interactions with a targeted receptor [127,128]. However, such approaches greatly alter the composition and behavior of EVs, both in the extracellular environment as well as following intracellular uptake, and the question is raised to what extent these approaches are advantageous over synthetic drug-loaded nanocarriers.…”

Section: Extracellular Behavior Of Evsmentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

157

103

View full text Add to dashboard Cite

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.

show abstract

PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time

Cited by 448 publications

References 68 publications

Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer

Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer

Towards Therapeutic Delivery of Extracellular Vesicles: Strategies for In Vivo Tracking and Biodistribution Analysis

Therapeutic and diagnostic applications of extracellular vesicles

Contact Info

Product

Resources

About