Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues

Emam, Sherif E.; Lila, Amr S. Abu; Elsadek, Nehal E.; Ando, Hidenori; Shimizu, Taro; Okuhira, Keiichiro; Ishima, Yu; Mahdy, Mahmoud A.; Ghazy, Fakhr-eldin S.; Ishida, Tatsuhiro

doi:10.1016/j.ejpb.2019.10.005

Cited by 49 publications

(37 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, some studies have indicated that exosomes can be used as carriers to carry anti-cancer drugs (Meng et al, 2020 ). Especially cancer cell-derived exosomes (Emam et al, 2019 ), i.e. autologous exosomes, were preferentially accumulated within tumor part compared to allogeneic exosomes, which showed good targeting property.…”

Section: Discussionmentioning

confidence: 99%

Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

et al. 2021

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is a highly lethal disease and the majority of NSCLC patients are desperate for therapies that can effectively target their cancer and ultimately improve their overall survival. Docetaxel (DTX) represents the first-line of the antitumor agent that is used to treat NSCLC; however, it has poor solubility in water and unsatisfactory encapsulation efficiency. In our study, exosomes were isolated from A549 cancer cells by ultracentrifugation and then characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB). The particle size changes of EXO and EXO-DTX were measured daily for seven days to test the stability. DTX was selected payload by electroporation (EXO-DTX). For the in vitro evaluation, cell proliferation, cell cycle, cell apoptosis, reactive oxygen species (ROS) assay and cellular uptake were evaluated in the A549 cells. Also, this study evaluated the target and therapeutic effect of DTX as an antitumor agent in vivo. As a result, EXO-DTX with a particle size of 149.5 nm were successfully prepared and the cytotoxicity of the EXO-DTX was much greater than that of DTX monomers. Exosomes significantly increased the cellular uptake in vitro evaluation and showed better targeting to tumor tissue compared to the free DTX in the mice. We also explored the potential of tumor cell-derived exosomes as a drug delivery agent to target the parent cancer. Hence, we conclude that exosomes might be used as a potential antitumor drug delivery system (DDS).

show abstract

Section: Discussionmentioning

confidence: 99%

Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The DSPE system is particularly well-suited for PEG functionalization of exosomal surfaces to improve the circulation lifetime in vivo. Eman et al have shown that PEGylated exosomes (PEG 2000 ) accumulated in murine colorectal cancer cell (C26)-tissue, leading to enhanced exosome uptake by the cancer cells and immune cells [64].…”

Section: Dspe or Other Hydrophobic Moiety Insertion Systemmentioning

confidence: 99%

Biofunctional Peptide-Modified Extracellular Vesicles Enable Effective Intracellular Delivery via the Induction of Macropinocytosis

Nakase

2021

Processes

View full text Add to dashboard Cite

We previously reported that macropinocytosis (accompanied by actin reorganization, ruffling of the plasma membrane, and engulfment of large volumes of extracellular fluid) is an important process for the cellular uptake of extracellular vesicles, exosomes. Accordingly, we developed techniques to induce macropinocytosis by the modification of biofunctional peptides on exosomal membranes, thereby enhancing their cellular uptake. Arginine-rich cell-penetrating peptides have been shown to induce macropinocytosis via proteoglycans; accordingly, we developed peptide-modified exosomes that could actively induce macropinocytotic uptake by cells. In addition, the activation of EGFR induces macropinocytosis; based on this knowledge, we developed artificial leucine-zipper peptide (K4)-modified exosomes. These exosomes can recognize E3 sequence-fused EGFR (E3-EGFR), leading to the clustering and activation of E3-EGFR by coiled-coil formation (E3/K4), which induces cellular exosome uptake by macropinocytosis. In addition, modification of pH-sensitive fusogenic peptides (e.g., GALA) also enhances the cytosolic release of exosomal contents. These experimental techniques and findings using biofunctional peptides have contributed to the development of exosome-based intracellular delivery systems.

show abstract

“…Compared with other vehicles, exosomes have better targeting ability. First, exosomes have been proved to have a weak homing effect, i.e., cancer-derived exosomes are preferentially absorbed by the cancer cells (65,101). Second, the exosomes originate from the cell membrane (4); thus, they can be modified via different targeted peptides or proteins and then can actively target cancer cells.…”

Section: Application In Overcoming Off-target Effectmentioning

confidence: 99%

Exosomes as Smart Nanoplatforms for Diagnosis and Therapy of Cancer

et al. 2021

View full text Add to dashboard Cite

Exosomes are composed of a lipid bilayer membrane, containing proteins, nucleic acids, DNA, RNA, etc., derived from donor cells. They have a size range of approximately 30-150 nm. The intrinsic characteristics of exosomes, including efficient cellular uptake, low immunogenicity, low toxicity, intrinsic ability to traverse biological barriers, and inherent targeting ability, facilitate their application to the drug delivery system. Here, we review the generation, uptake, separation, and purification methods of exosomes, focusing on their application as carriers in tumor diagnosis and treatment, especially in brain tumors, as well as the patent applications of exosomes in recent years.

show abstract

Cancer cell-type tropism is one of crucial determinants for the efficient systemic delivery of cancer cell-derived exosomes to tumor tissues

Cited by 49 publications

References 65 publications

Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Biofunctional Peptide-Modified Extracellular Vesicles Enable Effective Intracellular Delivery via the Induction of Macropinocytosis

Exosomes as Smart Nanoplatforms for Diagnosis and Therapy of Cancer

Contact Info

Product

Resources

About