Smart pH-sensitive nanoassemblies with cleavable PEGylation for tumor targeted drug delivery

Sci Rep. 2017 Jun 13;7(1):3383. doi: 10.1038/s41598-017-03111-2.

Abstract

A new acidly sensitive PEGylated polyethylenimine linked by Schiff base (PEG-s-PEI) was designed to render pH-sensitive PEGylation nanoassemblies through multiple interactions with indomethacin and docetaxel (DTX). DTX nanoassemblies driven by PEG-s-PEI thus formulated exhibited an excellent pH-sensitivity PEGylation cleavage performance at extracellular pH of tumor microenvironment, compared to normal tissues, thereby long circulated in blood but were highly phagocytosed by tumor cells. Consequently, this smart pH-sensitive PEGylation cleavage provided an efficient strategy to target tumor microenvironment, in turn afforded superior therapeutic outcome in anti-tumor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Cell Proliferation / drug effects*
  • Docetaxel / administration & dosage*
  • Docetaxel / chemistry
  • Docetaxel / pharmacokinetics
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Humans
  • Hydrogen-Ion Concentration
  • Indomethacin / administration & dosage
  • Indomethacin / chemistry
  • Indomethacin / pharmacokinetics
  • Male
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Polyethylene Glycols / chemistry*
  • Polyethyleneimine / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Docetaxel
  • Polyethylene Glycols
  • Polyethyleneimine
  • Indomethacin