Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 382-390, April 2010

Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas

  • Darya Alizadeh, MS

      Affiliations

    • Division of Neurosurgery, City of Hope National Cancer Center, Duarte, California, USA
    • ,
  • Leying Zhang, PhD

      Affiliations

    • Division of Neurosurgery, City of Hope National Cancer Center, Duarte, California, USA
    • ,
  • Jungyeon- Hwang, PhD

      Affiliations

    • Calando Pharmaceuticals, Pasadena, California, USA
    • ,
  • Thomas Schluep, ScD

      Affiliations

    • Calando Pharmaceuticals, Pasadena, California, USA
    • ,
  • Behnam Badie, MD

      Affiliations

    • Division of Neurosurgery, City of Hope National Cancer Center, Duarte, California, USA
    • Corresponding Author InformationCorresponding author:

Received 2 February 2009; accepted 1 October 2009. published online 16 October 2009.

Abstract 

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.

From the Clinical Editor

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.

Key words: Brain neoplasm, Central nervous system, Microglia, Nanoparticle

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 The senior author owns stocks in Arrowhead Research Inc, which is a part owner of Calando Pharmaceuticals.

 This work was supported by American Cancer Society Research Scholar Grant (RSG-03-142-01-CNE), the James S. McConnell Foundation, and Insert Therapeutics (to B. Badie). The City of Hope Flow Cytometry Core was equipped in part through funding provided by ONR N00014-02-1 0958, DOD 1435-04-03GT-73134, and NSF DBI-9970143.

PII: S1549-9634(09)00189-0

doi:10.1016/j.nano.2009.10.001

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 6, Issue 2 , Pages 382-390, April 2010

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