One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood-brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment.
Bibliographical noteFunding Information:
Acknowledgments This work was supported by the Health Sciences System of the Nevada System of Higher Education through the Inter-institutional Biomedical Research Activities Fund (IBRAF). Henry Hirschberg is grateful for the support of the Norwegian Ra-diumhospital Research Foundation. Portions of this work were made possible through access to the Laser Microbeam and Medical Program (LAMMP) and the Chao Cancer Center Optical Biology Shared Resource at the University of California, Irvine. The nanoshells were a generous gift from Nanospectra Biosciences, Inc.
- Blood brain barrier
- Gold nanoshells
- Nanoshell delivery
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research