Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo

J Drug Target. 2016;24(4):359-71. doi: 10.3109/1061186X.2015.1077850. Epub 2015 Aug 21.

Abstract

The high transfection efficiency and enhanced therapeutic effect of drug delivery systems developed in recent years imply that ligand-decorated nanocarriers are potentially targeted vectors for breast cancer treatment. Thioaptamer (TA)-modified nanoparticles (NPs) designed in this study mainly consisted of ligand TA and dendritic polyamidoamine (PAMAM). Knowing that TA can bind to CD44-receptors in breast cancer, this study was intended to validate the safety and feasibility of systemic miRNA delivery to breast cancer cells by TA-PEG-PAMAM/miRNA (polyethylene glycol - PEG), testify its tumor targeting efficiency in vitro, and observe its biodistribution when it was administered systemically to a xenograft mouse model of breast cancer. The in vivo and ex vivo imaging results in human breast cancer tumor-bearing mice showed that TA-modification was able to enhance the accumulation of NPs in the breast cancer tumor. Our data showed that TA-NPs did not induce functional impairment to normal tissues and vital organs. TA-NPs may prove to be a safe and effective miRNA deliver system for breast cancer treatment, and could be widely used in pre-clinical and eventually clinical arenas of breast cancer treatment.

Keywords: Breast cancer; CD44; microRNA; targeted delivery; thioaptamer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Aptamers, Nucleotide / chemistry*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dendrimers / chemistry
  • Drug Carriers / chemistry*
  • Endocytosis / drug effects
  • Female
  • Humans
  • Hyaluronan Receptors / genetics*
  • Hyaluronan Receptors / metabolism
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / genetics
  • Mice, Inbred BALB C
  • MicroRNAs / administration & dosage
  • MicroRNAs / genetics
  • MicroRNAs / pharmacokinetics
  • MicroRNAs / therapeutic use*
  • Microscopy, Fluorescence
  • Molecular Targeted Therapy
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Surface Properties
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • CD44 protein, human
  • Dendrimers
  • Drug Carriers
  • Hyaluronan Receptors
  • MIRN145 microRNA, human
  • MicroRNAs
  • PAMAM Starburst
  • Polyethylene Glycols