Dual Stimuli-Responsive Nanoparticles for Controlled Release of Anticancer and Anti-inflammatory Drugs Combination

Chemistry. 2017 Jul 12;23(39):9397-9406. doi: 10.1002/chem.201701524. Epub 2017 Jun 19.

Abstract

Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to augment therapeutic efficacy have become a promising tool for anticancer drug delivery. However, the rational design of these "smart" nanoparticles for a selective delivery and controlled release of multidrug combinations in cancer cells to achieve synergistic effects remain challenging. Here we report the pH/redox dual responsive nanoparticle FA-DOX-Ind-NP (FA=folic acid, DOX=doxorubicin, Ind=indomethacin, NP=nanoparticle) based on the novel tumor targeting and biodegradable poly(β-amino ester) polymer, and demonstrate its high ability to enter into cancer cells and release a combination of the anticancer drug doxorubicin and the non-steroidal anti-inflammatory drug indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome multidrug resistance. This study highlights the great potential of tumor targeting and dual stimuli-responsive nanoparticles for an efficient delivery of multidrug combination to improve the cancer therapeutic efficacy.

Keywords: anti-inflammatory drugs; anticancer drugs; controlled release; drug delivery; drug design.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / toxicity
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Folic Acid
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Indomethacin / chemistry
  • Indomethacin / metabolism
  • Interleukin-6 / metabolism
  • MCF-7 Cells
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Polymers / chemistry
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Drug Carriers
  • Interleukin-6
  • Polymers
  • Tumor Necrosis Factor-alpha
  • Doxorubicin
  • Folic Acid
  • Cyclooxygenase 2
  • Indomethacin