Co-delivery of docetaxel and curcumin prodrug via dual-targeted nanoparticles with synergistic antitumor activity against prostate cancer

Biomed Pharmacother. 2017 Apr:88:374-383. doi: 10.1016/j.biopha.2016.12.138. Epub 2017 Jan 22.

Abstract

Purpose: Combination therapy is increasingly used as a primary cancer treatment regimen. In this report, we designed EGFR peptide decorated nanoparticles (NPs) to co-deliver docetaxel (DTX) and pH sensitive curcumin (CUR) prodrug for the treatment of prostate cancer.

Results: EGFR peptide (GE11) targeted, pH sensitive, DTX and CUR prodrug NPs (GE11-DTX-CUR NPs) had an average diameter of 167nm and a zeta potential of -37.5mV. The particle size of the NPs was adequately maintained in serum and a sustained drug release pattern was observed. Improved inhibition of cancer cell and tumor tissue growth was shown in the GE11-DTX-CUR NPs group compared to the other groups.

Conclusion: It can be summarized that DTX and CUR prodrug could be delivered into tumor cells simultaneously by the GE 11 targeting and the EPR effect of NPs. The resulting GE11-DTX-CUR NPs is a promising system for the synergistic antitumor treatment of prostate cancer.

Keywords: Dual-targeted nanoparticles; EGFR-mediated endocytosis; Prostate cancer; Synergistic combination therapy; Targeted delivery system.

MeSH terms

  • Aconitic Acid / analogs & derivatives
  • Aconitic Acid / chemistry
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Coumarins / chemistry
  • Curcumin / chemistry
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Docetaxel
  • Drug Delivery Systems*
  • Drug Liberation
  • Drug Stability
  • Drug Synergism
  • Endocytosis / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Lactic Acid / chemistry
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Particle Size
  • Peptides / chemistry
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Prodrugs / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Proton Magnetic Resonance Spectroscopy
  • Taxoids / chemistry
  • Taxoids / pharmacology
  • Taxoids / therapeutic use*
  • Thiazoles / chemistry

Substances

  • Antineoplastic Agents
  • Coumarins
  • GE11 peptide
  • Peptides
  • Prodrugs
  • Taxoids
  • Thiazoles
  • coumarin 6
  • Docetaxel
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethylene Glycols
  • aconitic anhydride
  • Aconitic Acid
  • Curcumin