Enhanced cytotoxic activity of bile acid cisplatin derivatives by conjugation with gold nanoparticles.

This article explores the potential cytotoxic activity of bile-acid cisplatin derivatives like bisursodeoxycholate(ethylenediamine)platinum(II), PtU2, when conjugated with gold nanoparticles, being a promising alternative to cisplatin in the treatment of cancer due to their lower toxicity. For our purpose we analyzed the intracellular delivery ability of these compounds after conjugation with 20-nm gold nanoparticles (PtU2-AuNPs) in the MG63 (osteosarcoma) cell line. Same platinum uptake after incubation with PtU2 and PtU2-AuNPs-derivatives is associated with a higher cytotoxic activity in case of the platinum-gold nanoparticle conjugate, the overall IC50 of PtU2 being reduced more than 10 fold for these new conjugates. When conjugated with gold nanoparticles, this bile-acid derivative is more efficient than the platinum compound alone in terms of their cytotoxic activity.

[1]  Noelia Dasilva,et al.  Biomarker Discovery by Novel Sensors Based on Nanoproteomics Approaches , 2012, Sensors.

[2]  M. Pérez‐Andrés,et al.  Bisursodeoxycholate(ethylenediamine)platinum(II): a new autofluorescent compound. Cytotoxic activity and cell cycle analysis in ovarian and hematological cell lines. , 2008, Dalton transactions.

[3]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[4]  Yi-zhi Li,et al.  Platinum(II) compounds bearing bone-targeting group: synthesis, crystal structure and antitumor activity. , 2010, Chemical communications.

[5]  J. de Lapuente,et al.  In vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake. , 2012, Journal of nanoscience and nanotechnology.

[6]  Duane E. Prasuhn,et al.  The controlled display of biomolecules on nanoparticles: a challenge suited to bioorthogonal chemistry. , 2011, Bioconjugate chemistry.

[7]  Manuel Fuentes,et al.  Nanotechniques in proteomics: protein microarrays and novel detection platforms. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[8]  Dakrong Pissuwan,et al.  The forthcoming applications of gold nanoparticles in drug and gene delivery systems. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[9]  A. Órfão,et al.  Intrinsically fluorescent cytotoxic cisplatin analogues as DNA marker molecules. , 2005, Bioconjugate chemistry.

[10]  Sarit S. Agasti,et al.  Gold nanoparticles in chemical and biological sensing. , 2012, Chemical reviews.

[11]  O. Moșteanu,et al.  Gold nanoparticles conjugated with cisplatin/doxorubicin/capecitabine lower the chemoresistance of hepatocellular carcinoma-derived cancer cells. , 2012, Journal of gastrointestinal and liver diseases : JGLD.

[12]  V. Rotello,et al.  Monolayer coated gold nanoparticles for delivery applications. , 2012, Advanced drug delivery reviews.

[13]  R K Jain,et al.  Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. , 1995, Cancer research.

[14]  R. Murray,et al.  Monolayer-protected cluster molecules. , 2000, Accounts of chemical research.

[15]  C. Giandomenico,et al.  Current status of platinum-based antitumor drugs. , 1999, Chemical reviews.

[16]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.