期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 11, 期 6, 页码 1365-1375出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.04.001
关键词
Gold nanoparticles; Doxorubicin; Melanoma; B16; Apoptosis; Necrosis; in vivo; Intratumoral; Allograft; Xenograft
资金
- NSERC/CIHR CHRP [385909-10]
- MDEIE [PSR-SIIRI-562]
- NSERC Individual Discovery RGPIN [312970-2013]
- CIHR [MOP-115195]
- FRSQ doctoral award
- Canada Research Chairs
Intratumoral injection of ultra-small gold nanoparticles (AuNPs) conjugated to doxorubicin (Au-Dox) is effective against both murine B16 and human SK-MEL-28 tumors in mice. Au-Dox suppresses growth of B16 tumors in immunocompetent mice by >70% for at least 19 days. In SK-MEL-28 xenografts, Au-Dox suppresses tumor growth almost completely for >13 weeks, while tumors treated with Dox alone demonstrate accelerated growth after 10 weeks. Histological analysis shows significant apoptosis and necrosis in Au-Dox treated tumors. Intratumoral injection is significantly more effective than intravenous injection, which leads to significant accumulation in liver and kidney with sub-therapeutic concentrations of Au-Dox. However, IV injection does not lead to significant damage in non-target organs, so improved targeting should permit this mode of delivery with little risk of systemic toxicity. The current construct is suitable for tumors accessible to intratumoral injection and represents a viable approach doxorubicin-resistant solid tumors. (C) 2015 Elsevier Inc. All rights reserved.
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