Combination of drug-conjugated SWCNT nanocarriers for efficient therapy of cancer stem cells in a breast cancer animal model

J Control Release. 2016 Mar 10:225:240-51. doi: 10.1016/j.jconrel.2016.01.053. Epub 2016 Jan 29.

Abstract

Targeting breast cancer and more specifically cancer stem cell (CSC) subpopulation, responsible for tumor growth, resistance and self-renewal, using combination of therapeutic drugs selectively delivered via biocompatible nanocarriers, provides a novel approach for effective therapy. Here, we propose to evaluate the potential therapeutic efficacy of combining Paclitaxel and Salinomycin drugs actively targeted to both breast cancer and CSCs in xenograft murine model after conjugation with biocompatible CD44 antibody conjugated SWCNTs via hydrazone linker allowing pH-responsive release mechanism near the acidic tumor microenvironment. Both in vitro investigations on MDA-MB-231, sorted CSC negative or CSC positive fractions and in vivo evaluations on tumor-bearing mice using noninvasive bioluminescence and magnetic resonance imaging confirmed the enhanced therapeutic effect of the combined therapy compared to treatment with individual drug-conjugated nanocarriers or free drug suspensions. Thus, confirmed the great promise of the developed SWCNTs drug delivery system for effective breast cancer treatment by targeting and eradicating both whole tumor cells and CSCs populations.

Keywords: Breast cancer stem cells; Drug delivery system; Noninvasive imaging; Paclitaxel; Salinomycin; Single walled carbon nanotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage*
  • Antibodies / chemistry
  • Antibodies / therapeutic use
  • Antigens, Tumor-Associated, Carbohydrate / blood
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Carriers / therapeutic use
  • Female
  • Humans
  • Hyaluronan Receptors / immunology
  • Hydrazones / administration & dosage
  • Hydrazones / chemistry
  • Hydrazones / therapeutic use
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mucin-1 / blood
  • Nanotubes, Carbon* / chemistry
  • Neoplastic Stem Cells / drug effects
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / therapeutic use
  • Pyrans / administration & dosage*
  • Pyrans / chemistry
  • Pyrans / therapeutic use
  • Tumor Burden / drug effects

Substances

  • Antibodies
  • Antigens, Tumor-Associated, Carbohydrate
  • Antineoplastic Agents
  • CA 27-29 antigen
  • Drug Carriers
  • Hyaluronan Receptors
  • Hydrazones
  • Mucin-1
  • Nanotubes, Carbon
  • Pyrans
  • salinomycin
  • Paclitaxel