Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas.
The goal of this study was to evaluate the mechanism of cyclodextrin-based nanoparticle (CDP-NP) uptake into a murine glioma model. Using mixed in vitro culture systems, we demonstrated that CDP-NPs were preferentially taken up by BV2 and N9 microglia (MG) cells compared with GL261 glioma cells. Fluorescent microscopy and flow cytometry analysis of intracranial GL261 gliomas confirmed these findings and demonstrated a predominant CDP-NP uptake by macrophages (MPs) and MG within and around the tumor site. Notably, in mice bearing bilateral intracranial tumor, MG and MPs carrying CDP-NPs were able to migrate to the contralateral tumors. In conclusion, these studies better characterize the cellular distribution of CDP-NPs in intracranial tumors and demonstrate that MPs and MG could potentially be used as nanoparticle drug carriers into malignant brain tumors.


BACKGROUND
The goal of this study was to evaluate the mechanism of cyclodextrin-based nanoparticle (CDP-NP) uptake into a murine glioma model. CDP-NP was preferentially taken up microglia (MG) cells as compared to glioma cells. A predominant CDP-NP uptake by macrophages and MG was also shown in and around the tumor site. Macrophages and MG could potentially be used as nanoparticle drug carriers into malignant brain tumors.
Alizadeh
Darya
D
Division of Neurosurgery, City of Hope National Cancer Center, Duarte, California, USA.
Zhang
Leying
L
Hwang
Jungyeon
J
Schluep
Thomas
T
Badie
Behnam
B
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use
D003505:Cyclodextrins; D004337:Drug Carriers