Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles

Int J Mol Sci. 2019 Nov 1;20(21):5458. doi: 10.3390/ijms20215458.

Abstract

The available and effective therapeutic means to treat choriocarcinoma is seriously lacking, mainly due to the toxic effects caused by chemotherapy and radiotherapy. Accordingly, we developed a method for targeting delivery of chemotherapeutical drugs only to cancer cells, not normal cells, in vivo, by using a synthetic placental chondroitin sulfate (CSA)-binding peptide (plCSA-BP) derived from malarial protein VAR2CSA. A 28 amino acids placental CSA-binding peptide (plCSA-BP) from the VAR2CSA was synthesized as a guiding peptide for tumor-targeting delivery, dendrigraft poly-L-lysines (DGL) was modified with plCSA-BP and served as a novel targeted delivery carrier. Choriocarcinoma was selected to test the effect of targeted delivery carrier, and prodigiosin isolated from Serratia marcescens subsp. lawsoniana was selected as a chemotherapeutical drug and encapsulated in the DGL modified by the plCSA-BP nanoparticles (DGL/CSA-PNPs). DGL/CSA-PNPs had a sustained slow-release feature at pH 7.4, which could specifically bind to the JEG3 cells and exhibited better anticancer activity than that of the controls. The DGL/CSA-PNPs induced the apoptosis of JEG3 cells through caspase-3 and the P53 signaling pathway. DGL/CSA-PNPs can be used as an excellent targeted delivery carrier for anticancer drugs, and the prodigiosin could be an alternative chemotherapeutical drug for choriocarcinoma.

Keywords: Serratia marcescens prodigiosin; choriocarcinoma; dendrigraft poly-l-lysines nanoparticles; placenta chondroitin sulfate A binding peptide; targeted delivery.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Chondroitin Sulfates / chemistry
  • Choriocarcinoma / metabolism
  • Choriocarcinoma / pathology*
  • Drug Compounding
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Humans
  • Nanoparticles / chemistry*
  • Peptides / chemistry*
  • Polylysine / chemistry*
  • Prodigiosin / administration & dosage
  • Prodigiosin / chemistry
  • Prodigiosin / pharmacokinetics*
  • Reproducibility of Results

Substances

  • Antineoplastic Agents
  • Peptides
  • Polylysine
  • Chondroitin Sulfates
  • Prodigiosin