Lasers Med Sci DOI 10.1007/s10103-015-1742-5
ORIGINAL ARTICLE
Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment Steen J. Madsen 1 & Catherine Christie 2,4 & Seok Jin Hong 3,4 & Anthony Trinidad 4 & Qian Peng 5 & Francisco A. Uzal 6 & Henry Hirschberg 1,4
Received: 24 July 2014 / Accepted: 9 March 2015 # Springer-Verlag London 2015
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-(3carboxymethoxyphenyl)-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. Keywords Glioma . Photothermal therapy . Gold–silica nanoshells . Rat macrophages
Introduction * Steen J. Madsen [email protected] 1
Department of Health Physics and Diagnostic Sciences, University of Nevada, 4505 South Maryland Pkwy, Las Vegas, NV 89154, USA
2
Department of Neurosurgery, University of California, Irvine, CA 92612, USA
3
Department of Otorhinolaryngology–Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
4
Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612, USA
5
Pathology Clinic, Rikshospitalet–Radiumhospitalet HF Medical Center, University of Oslo, Montebello, Oslo N–0310, Norway
6
School of Veterinary Medicine, University of California, Davis, San Bernardino, CA, USA
Primary brain tumors are neoplasms that originate from the parenchymal elements of the brain. There are approximately 17,000 new cases of primary brain tumors diagnosed within the USA every year and an equal number in the EU region [1]. Approximately 40 % of these are of the most malignant variety, glioblastoma multiforme (GBM). Five-year survival rates are dismal (
ORIGINAL ARTICLE
Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment Steen J. Madsen 1 & Catherine Christie 2,4 & Seok Jin Hong 3,4 & Anthony Trinidad 4 & Qian Peng 5 & Francisco A. Uzal 6 & Henry Hirschberg 1,4
Received: 24 July 2014 / Accepted: 9 March 2015 # Springer-Verlag London 2015
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-(3carboxymethoxyphenyl)-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. Keywords Glioma . Photothermal therapy . Gold–silica nanoshells . Rat macrophages
Introduction * Steen J. Madsen [email protected] 1
Department of Health Physics and Diagnostic Sciences, University of Nevada, 4505 South Maryland Pkwy, Las Vegas, NV 89154, USA
2
Department of Neurosurgery, University of California, Irvine, CA 92612, USA
3
Department of Otorhinolaryngology–Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
4
Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612, USA
5
Pathology Clinic, Rikshospitalet–Radiumhospitalet HF Medical Center, University of Oslo, Montebello, Oslo N–0310, Norway
6
School of Veterinary Medicine, University of California, Davis, San Bernardino, CA, USA
Primary brain tumors are neoplasms that originate from the parenchymal elements of the brain. There are approximately 17,000 new cases of primary brain tumors diagnosed within the USA every year and an equal number in the EU region [1]. Approximately 40 % of these are of the most malignant variety, glioblastoma multiforme (GBM). Five-year survival rates are dismal (
