Development of synthetic high-density lipoprotein-based ApoA-I mimetic peptide-loaded docetaxel as a drug delivery nanocarrier for breast cancer chemotherapy

Drug Deliv. 2019 Dec;26(1):708-716. doi: 10.1080/10717544.2019.1618420.

Abstract

In this study, a synthetic high-density lipoprotein (sHDL), peptide-based nanocarrier loaded with docetaxel (DTX) was constructed, against breast cancer. The thermodynamic and molecular dynamic analyses were conducted to examine the stability of nanoparticles synthesized from mimetic peptide 5 A and various types of phospholipids. Furthermore, the cellular uptake and in vivo fluorescence imaging analysis experiments, with scavenger receptor B-I (SR-BI) were carried out to examine the tumor-targeting ability of sHDL. The nanoparticles were investigated for their pharmacodynamic and cytotoxic effects to show their effectivity as anti-tumor agents. The results showed that the synthesized sHDL nanoparticles exhibited a high payload of DTX, sustained drug release properties, and excellent biocompatibility. Moreover, DTX-sHDL nanoparticles enhanced the uptake of DTX, increased the cytotoxicity against MCF-7 cells, and reduced the off-target side-effects to normal cells. Finally, experiments in 4T1 cell line-bearing mice indicate that inhibition of tumor growth by DTX-sHDL nanoparticles was superior to that of free DTX group. Thus, the sHDL nanoparticles are a promising drug delivery vehicle for improving the efficacy of anti-cancer drugs.

Keywords: Synthetic high-density lipoprotein; anticancer; breast cancer; docetaxel; mimetic peptide.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apolipoprotein A-I / chemistry*
  • Biomimetic Materials
  • Delayed-Action Preparations
  • Docetaxel / administration & dosage*
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use
  • Docetaxel / toxicity
  • Drug Carriers / chemistry*
  • Epithelial Cells
  • Female
  • Humans
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Optical Imaging
  • Peptides / chemistry
  • Scavenger Receptors, Class B / metabolism

Substances

  • Antineoplastic Agents
  • Apolipoprotein A-I
  • Delayed-Action Preparations
  • Drug Carriers
  • Peptides
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Docetaxel

Grants and funding

This work was supported by the National Natural Science Foundation of China [No. 51603128]; Shenyang Key Laboratory Project of Functional Drug Carrier Materials financed by Shenyang Technology Council [No. S180062], Education Department Project of Liaoning Province[No. L2015527] and Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University [No. ZQN2016012].