Intratumoral gold-doxorubicin is effective in treating melanoma in mice

• Published in: Nanomedicine 2015-08, Vol.11 (6), p.1365-1375
• Main Authors: Zhang, Xuan, B.S, Teodoro, Jose G., PhD, Nadeau, Jay L., PhD
• Format: Article
• Language: English
• Subjects: Allograft; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - therapeutic use; Apoptosis; B16; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Drug Delivery Systems; Gold - administration & dosage; Gold - pharmacokinetics; Gold - therapeutic use; Gold nanoparticles; Heterografts; In Situ Nick-End Labeling; in vivo; Injections, Intralesional; Internal Medicine; Intratumoral; Melanoma; Melanoma, Experimental - drug therapy; Mice; Necrosis; Tissue Distribution; Xenograft
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.04.001

Abstract 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. From the Clinical Editor Drug resistance is a significant problem in the fight against cancer. The authors describe a new approach in combating drug resistance in tumor cells by conjugating ultrasmall gold nanoparticles to doxorubicin. They tested the efficacy in in-vivo models using two melanoma cell lines. The promising results obtained from intra-tumoral injections contribute a way in future drug designs showing that conjugation to nanoparticles could lead to more effective and synergistic killing of tumor cells.