Tumor targeting and microenvironment-responsive nanoparticles for gene delivery

Shixian Huang, Kun Shao, Yuyang Kuang, Yang Liu, Jianfeng Li, Sai An, Yubo Guo, Haojun Ma, Xi He, Chen Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

A tumor targeting nanoparticle system has been successfully developed to response to the lowered tumor extracellular pH (pHe) and upregulated matrix metalloproteinase 2 (MMP2) in the tumor microenvironment. The nanoparticles are modified with activatable cell-penetrating peptide (designated as dtACPP) that's dual-triggered by the lowered pHe and MMP2. In dtACPP, the internalization function of cell-penetrating peptide (CPP) is quenched by a pH-sensitive masking peptide, linking by a MMP2 substrate. The masking peptide is negatively charged to quench the cationic CPP well after systemic administration. Hence, dtACPP-modified nanoparticles possesses passive tumor targetability via the enhanced permeability and retention (EPR) effect. Once reaching the tumor microenvironment, the pre-existing attraction would be eliminated due to the lowered pHe, accompanying the linker cleaved by MMP2, dtACPP would be activated to expose CPP to drive the nanoparticles' internalization into the intratumoral cells. The studies of plasmid DNA loading, toxicity assessment, cellular uptake, tumor targeting delivery, and gene transfection demonstrate that dtACPP-modified nanoparticle system is a potential candidate for tumor targeting gene delivery.

Original languageEnglish (US)
Pages (from-to)5294-5302
Number of pages9
JournalBiomaterials
Volume34
Issue number21
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Activatable
  • Cell-penetrating peptide
  • Gene delivery
  • Tumor microenvironment
  • Tumor targeting nanoparticles

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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