Jump to main content
Jump to site search

Issue 4, 2020

Engineering microglia as intraoperative optical imaging agent vehicles potentially for fluorescence-guided surgery in gliomas

Author affiliations

Abstract

Surgical resection currently remains the mainstay of treatment for patients with gliomas of any grade. The maximum extent of surgical resection is associated with a long-term disease control; however, maximal resection of the brain tumor possibly results in additional neurological deficits. Therefore, improving the precision in brain tumor surgery by visual identification and screening of tumor cells can help to tackle this devastating disease. In the present study, BV2 microglial cells were engineered by iron oxide-nanoparticle stimulation as intraoperative optical imaging agent vehicles and loaded with near-infrared fluorescent dye DiD (DiDBV2-Fe) potentially for fluorescence-guided brain tumor surgery. Activation of BV2 microglial cells by citrate-stabilized iron oxide nanoparticles at a concentration of 62.5 μg mL−1 significantly inhibited M2 markers (arginase-1 and CD206), which is able to minimize risks of the immunosuppressive effects caused by the M2-like phenotype of microglial cells. Meanwhile, activated BV2 microglial cells showed up-regulation of arylsulfatase A, apolipoprotein E, transferrin, and ferritin heavy chain-1 gene expression that tends to promote microglia transport across the blood–brain barrier (BBB). Compared to DiDBV2 without iron oxide activation, DiDBV2-Fe indicated strong tumor tropism in response to monocyte chemoattractant protein-1 (CCL2) secreted by U87MG tumor cells. In vivo experiments proved that DiDBV2-Fe efficiently crossed the BBB and more than 90% fluorescence intensity generated by activated microglial cells was detected in the brain when administered through the carotid artery in an orthotopic glioblastoma mouse model. Notably, DiDBV2-Fe produced clear tumor border demarcation on near-infrared imaging and exhibited a superior tumor-to-brain fluorescence ratio to commercial 5-aminolevulinic acid. Accumulated DiDBV2-Fe induced a strong fluorescence signal in brain tumor tissue for a prolonged period (4–24 h), which is beneficial to perform complex and time-consuming brain operations. Overall, our study suggests that this newly engineered microglial cell has promise for enabling more accurate brain tumor imaging for fluorescence-guided resections.

Graphical abstract: Engineering microglia as intraoperative optical imaging agent vehicles potentially for fluorescence-guided surgery in gliomas

Supplementary files

Article information


Submitted
03 Sep 2019
Accepted
16 Oct 2019
First published
04 Nov 2019

Biomater. Sci., 2020,8, 1117-1126
Article type
Paper

Engineering microglia as intraoperative optical imaging agent vehicles potentially for fluorescence-guided surgery in gliomas

L. Guo, X. Zhang, R. Wei, G. Li, B. Sun, H. Zhang, D. Liu, C. Wang and M. Feng, Biomater. Sci., 2020, 8, 1117 DOI: 10.1039/C9BM01388A

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

Search articles by author

Spotlight

Advertisements