Issue 6, 2022

Extracellular vesicle-mediated co-delivery of TRAIL and dinaciclib for targeted therapy of resistant tumors

Abstract

Extracellular vesicle (EV) delivery of TNF-related apoptosis-inducing ligand (TRAIL) (EV-T) has been shown to be highly efficient for cancer treatment when combined with the potent cyclin-dependent kinase (CDK) inhibitor dinaciclib (SCH727965, Dina). However, only topical administration was previously tested for cancer treatment, leaving unknown the efficacy of systemic therapy by EV-T and Dina. In this study we hypothesize that the systemic application of EV-T and Dina can be performed through EV-mediated co-delivery of TRAIL and Dina. Dina was first post-loaded into EV-Ts by sonication to prepare EV-mediated co-delivery of TRAIL and Dina, designated Dina@EV-T. Then Dina@EV-Ts were shown to be stable, readily endocytosed into cancer cells, and highly effective at inducing intensive apoptosis in resistant cancer lines but not in normal cells. Moreover, systemically infused Dina@EV-Ts showed evident tumor tropism suggesting their good potential for tumour-targeted delivery of therapeutics. Importantly, the systemic therapy with Dina@EV-Ts showed the best efficacy in vivo when compared with other treatments. The augmented therapeutic efficacy appeared to be associated with the concomitant suppression of prosurvival CDK1 and anti-apoptotic proteins including CDK9, cFLIP, MCL-1, BCL-2 and Survivin by Dina@EV-T treatment. Additionally, there were no adverse side effects observed for the systemic Dina@EV-T therapy. In conclusion, our data suggest that the co-delivery of TRAIL and Dina by EVs potentially constitutes a novel tumour-targeted therapy, which is highly effective and safe for the treatment of refractory tumors.

Graphical abstract: Extracellular vesicle-mediated co-delivery of TRAIL and dinaciclib for targeted therapy of resistant tumors

Supplementary files

Article information

Article type
Paper
Submitted
17 Nov 2021
Accepted
24 Jan 2022
First published
28 Jan 2022

Biomater. Sci., 2022,10, 1498-1514

Extracellular vesicle-mediated co-delivery of TRAIL and dinaciclib for targeted therapy of resistant tumors

C. Ke, H. Hou, K. Su, C. Huang, Q. Yuan, S. Li, J. Sun, Y. Lin, C. Wu, Y. Zhao and Z. Yuan, Biomater. Sci., 2022, 10, 1498 DOI: 10.1039/D1BM01751A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements