A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy

Int J Pharm. 2016 May 30;505(1-2):96-106. doi: 10.1016/j.ijpharm.2016.03.025. Epub 2016 Mar 17.

Abstract

A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by-Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug-loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy.

Keywords: Au nanoparticles; Chemo-photothermal therapy; Layered double hydroxide; Methotrexate.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / therapy
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / chemistry
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Drug Delivery Systems
  • Drug Liberation
  • Gold / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Hyperthermia, Induced*
  • Lung Neoplasms / therapy
  • Metal Nanoparticles*
  • Methotrexate / administration & dosage*
  • Methotrexate / chemistry
  • Methotrexate / pharmacology
  • Polyethylenes / chemistry
  • Quaternary Ammonium Compounds / chemistry

Substances

  • Antimetabolites, Antineoplastic
  • Polyethylenes
  • Quaternary Ammonium Compounds
  • poly-N,N-dimethyl-N,N-diallylammonium chloride
  • Gold
  • Methotrexate