A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy

Nano Lett. 2015 Jan 14;15(1):457-63. doi: 10.1021/nl503777s. Epub 2014 Dec 12.

Abstract

The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver-gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells.

Keywords: Nuclear uptake; aptamer; cell-targeted delivery; drug-resistant cancer therapy; photocontrollable size.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Aptamers, Nucleotide* / chemistry
  • Aptamers, Nucleotide* / pharmacology
  • Cell Line, Tumor
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacology
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Gold / chemistry
  • Humans
  • Metal Nanoparticles / chemistry*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Silver / chemistry

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Drug Carriers
  • Silver
  • Gold