Oligonucleotides--assembled Au nanorod-assisted cancer photothermal ablation and combination chemotherapy with targeted dual-drug delivery of Doxorubicin and Cisplatin prodrug

ACS Appl Mater Interfaces. 2014 Mar 26;6(6):4382-93. doi: 10.1021/am5000905. Epub 2014 Mar 5.

Abstract

External stimuli responsive dual drugs carrier was synthesized with Au nanorods (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5' thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into the duplexes. The cDNA designed with the 5' amine functional group assisted to tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated with the folic acid (FA) to target folate receptors overexpressed in the cancer cells. This targeting vehicle provided remote-controlled delivery of this high toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm diode laser irradiation. The dehybridization set the Dox free to bind the cell nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an active drug. The in vitro and in vivo studies revealed that this external stimulus responsive combination drug delivery was significantly effective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Cisplatin / administration & dosage*
  • Cisplatin / chemistry
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Carriers / chemistry
  • Drug Delivery Systems / instrumentation*
  • Drug Delivery Systems / methods
  • Folate Receptors, GPI-Anchored / antagonists & inhibitors
  • Folate Receptors, GPI-Anchored / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Nanotubes / chemistry
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oligonucleotides / chemistry*
  • Phototherapy*
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Folate Receptors, GPI-Anchored
  • Oligonucleotides
  • Prodrugs
  • Doxorubicin
  • Cisplatin