期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 10, 期 7, 页码 1205-1216出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2014.1855
关键词
Glucose Capped Gold Nanoparticles (Glu-GNPs); Pegylated Glu-GNPs (PEG-Glu-GNPs); Pharmacokinetics of Gold-Based Nanoparticles; Enhanced Radiotherapy
资金
- National Natural Science Foundation of China
- National Research Council/National Institute of Nanotechnology, Canada
- Canadian Cancer Research Alliance
Pharmacokinetics and bio-distribution are crucial factors affecting the performance of an intravenous drug. In this study, we explore the combined use of glucose and polyethylene glycol (PEG) ligands to further improve gold nanoparticle (GNP) pharmacokinetics and bio-distribution, with the aim of using the drug for in-vivo radiotherapy. The inclusion of PEG was found to significantly prolong the half-life period, where PEG-Glu-GNPs achieved 6.17 +/- 3.71 h, compared to 1.23 +/- 0.14 h for Glu-GNPs and 1.07 +/- 0.22 h for uncoated GNPs. Our data indicates that nanoparticle size impacts cell uptake performance, with 20 nm being the optimal diameter for cancer treatment applications. Although PEG-Glu-GNPs mainly distributed in the spleen, liver, lung, and kidneys, the concentration of PEG-Glu-GNPs in tumour tissue was 20 times higher than healthy cells in the uterus and ovaries, reaching 9.22 +/- 2.41 mu g/g cancer tissue at 48 h after injection. This difference in uptake holds promise for selective tumor targeting which can in turn lead to more effective radiotherapy through the interaction of X-rays and GNPs. Specifically tumor size after 47 days of treatment had reduced to (769 +/- 92) mm(3) compared to (1432 +/- 269) mm(3) using X-rays alone and (3514 +/- 1818) mm(3) without any treatment. Moreover, the mice remained healthy without statistically significant weight loss. Results of our pharmacokinetic and bio-distribution study as well as therapeutic data for PEG-Glu-GNPs in our tumor bearing animal model demonstrate that PEG-Glu-GNPs provide excellent in-vivo stability, tumor targeting function, and radiotherapeutic enhancement effects, providing useful insights for further clinical studies.
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