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Extracellular vesicles derived from dendritic cells loaded with VEGF-A siRNA and doxorubicin reduce glioma angiogenesis in vitro

Shamshiripour, Parisa, Rahnama, Mehrana, Nikoobakht, Mehdi, Rad, Vahideh Farzam, Moradi, Ali-Reza, Ahmadvand, Davoud·2024·Journal of Controlled Release
DOI 10.1016/j.jconrel.2024.03.042
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Abstract

Background Numerous attempts have been devoted to designing anti-angiogenic agents as a strategy to slow tumor growth and progression. Clinical applications of conventional anti-angiogenic agents face some challenges, e.g., off-target effects for TKIs and also low solid tumor penetration for mAbs. Furthermore, although anti-angiogenic therapy provides a normalization window for better chemo-RT response, in long-term treatments, tumor hypoxia as a result of total removal of VEGF-A by mAbs from the TME or complete blockade of TK receptors induces over-activation of compensatory angiogenic pathways, causing escape. Herein, we investigate the efficacy of si-DOX-DC-EVs to reduce glioma angiogenesis and invasiveness. Methods Mature DCs were generated from PBMC and EVs were isolated from the DCs culture media. siRNA and Doxorubicin were loaded into EVs by EP and incubation. Afterward, the uptake of DC-EVs was assessed by flow cytometry, and the subcellular localization of EVs was tested by confocal imaging. Tube formation assay was performed to assess the efficacy of si-DOX-DC-EVs to reduce tumor angiogenesis which was analyzed by DHM. Morphometric analysis of apoptotic cells was performed by DHM and confocal imaging and further, ELISA was performed for hypoxia-related and angiogenic cytokines. The impact of our theranostic system "si-DOX-DC-MVs" on the formation of vascular mimics, colonies, and invasion of C6 cells was checked in vitro. Afterward, orthotropic rat models of glioma…

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Metadata

Authors
Shamshiripour, P., Rahnama, M., Nikoobakht, M., Rad, V. F., Moradi, A.-R., & Ahmadvand, D.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2024-05
Volume
369
Pages
128-145
ISSN
0168-3659
DOI
10.1016/j.jconrel.2024.03.042
Cited by
45
References
2
Language
en
Licence
Funders
  • National Foundation of Elites (25025)
  • Iran University of Medical Sciences
  • National Institute for Medical Research Development (973,168)

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