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Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment

Lasers in Medical Science volume 30, pages 1357–1365 (2015)Cite this article

Abstract

Gold-based nanoparticles have been used in a number of therapeutic and diagnostic applications. The purpose of this study was to investigate the efficacy of gold–silica nanoshells (AuNS) in photothermal therapy (PTT) of rat gliomas. Rat alveolar macrophages (Ma) were used as nanoparticle delivery vectors. Uptake of AuNS (bare and PEGylated) was investigated in Ma. AuNS were incubated with Ma for 24 h. Phase contrast microscopy was used to visualize the distribution of loaded Ma in three-dimensional glioma spheroids. PTT efficacy was evaluated for both empty (Ma) and AuNS-loaded Ma (MaNS) in both monolayers and spheroids consisting of C6 rat glioma cells and Ma. Monolayers/spheroids were irradiated for 5 min with light from an 810-nm diode laser at irradiances ranging from 7 to 28 W cm−2. Monolayer survival was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay while PTT efficacy in spheroids was determined from growth kinetics and live/dead fluorescence microscopy. PTT efficacy was investigated in vivo using a Sprague–Dawley rat glioma model. Five rats received direct intracranial injection of a mixture of 104 C6 glioma cells and, 2 days later, an equal number of MaNS. Three rats received laser treatment (810 nm; 10 min; 1 W) while the remaining two served as controls (no laser treatment). The uptake ratio of bare to PEGylated AuNS by Ma was 4:1. A significant photothermal effect was observed in vitro, albeit at relatively high radiant exposures (2.1–4.2 kJ cm−2). PTT proved effective in vivo in preventing or delaying tumor development in the PTT-treated animals.

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Acknowledgments

The authors are grateful for support from the Norwegian Radium Hospital Research Foundation. Portions of this work were made possible through access to the LAMMP Program NIBIB P41EB015890 and the Chao Cancer Center Optical Biology Shared Resource at UCI. Steen Madsen was supported, in part, by the Tony and Renee Marlon Charitable Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All animal studies were approved by the Institutional Animal Care and Use Committee at the University of California, Irvine, and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The manuscript does not contain clinical studies or patient data.

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Authors and Affiliations

  1. Department of Health Physics and Diagnostic Sciences, University of Nevada, 4505 South Maryland Pkwy, Las Vegas, NV, 89154, USA

    Steen J. Madsen & Henry Hirschberg

  2. Department of Neurosurgery, University of California, Irvine, CA, 92612, USA

    Catherine Christie

  3. Department of Otorhinolaryngology–Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    Seok Jin Hong

  4. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, 92612, USA

    Catherine Christie, Seok Jin Hong, Anthony Trinidad & Henry Hirschberg

  5. Pathology Clinic, Rikshospitalet–Radiumhospitalet HF Medical Center, University of Oslo, Montebello, Oslo, N–0310, Norway

    Qian Peng

  6. School of Veterinary Medicine, University of California, Davis, San Bernardino, CA, USA

    Francisco A. Uzal

Authors
  1. Steen J. Madsen
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  2. Catherine Christie
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  3. Seok Jin Hong
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  4. Anthony Trinidad
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  5. Qian Peng
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  6. Francisco A. Uzal
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  7. Henry Hirschberg
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Correspondence to Steen J. Madsen.

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Madsen, S.J., Christie, C., Hong, S.J. et al. Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment. Lasers Med Sci 30, 1357–1365 (2015). https://doi.org/10.1007/s10103-015-1742-5

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  • DOI: https://doi.org/10.1007/s10103-015-1742-5

Keywords

  • Glioma
  • Photothermal therapy
  • Gold–silica nanoshells
  • Rat macrophages

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