title: Intratumoral gold-doxorubicin is effective in treating melanoma in mice.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Biomedical Engineering, McGill University, Montreal QC Canada.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, McGill University, Montreal QC Canada; Goodman Cancer Research Centre, McGill University, Montreal QC Canada.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Teodoro
authors.affiliation: Department of Biomedical Engineering, McGill University, Montreal QC Canada. Electronic address: jay.nadeau@mcgill.ca.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Nadeau
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D064593:Heterografts; D020287:In Situ Nick-End Labeling; D015552:Injections, Intralesional; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D006046:Gold; D004317:Doxorubicin
keywords: Allograft; Apoptosis; B16; Doxorubicin; Gold nanoparticles; Intratumoral; Melanoma; Necrosis; Xenograft; in vivo