Cell-Penetrating Poly(disulfide) Assisted Intracellular Delivery of Mesoporous Silica Nanoparticles for Inhibition of miR-21 Function and Detection of Subsequent Therapeutic Effects

Angew Chem Int Ed Engl. 2016 Aug 1;55(32):9272-6. doi: 10.1002/anie.201602188. Epub 2016 Jun 21.

Abstract

The design of drug delivery systems capable of minimal endolysosomal trapping, controlled drug release, and real-time monitoring of drug effect is highly desirable for personalized medicine. Herein, by using mesoporous silica nanoparticles (MSNs) coated with cell-penetrating poly(disulfide)s and a fluorogenic apoptosis-detecting peptide (DEVD-AAN), we have developed a platform that could be uptaken rapidly by mammalian cells via endocytosis-independent pathways. Subsequent loading of these MSNs with small molecule inhibitors and antisense oligonucleotides resulted in intracellular release of these drugs, leading to combination inhibition of endogenous miR-21 activities which was immediately detectable by the MSN surface-coated peptide using two-photon fluorescence microscopy.

Keywords: cell-penetrating poly(disulfide); drug delivery; endocytosis; nanoparticles; small-molecule inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell-Penetrating Peptides / chemistry*
  • Disulfides / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • HeLa Cells
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism
  • Microscopy, Fluorescence
  • Molecular Structure
  • Nanoparticles / chemistry
  • Silicon Dioxide / chemistry
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Cell-Penetrating Peptides
  • Disulfides
  • MIRN21 microRNA, human
  • MicroRNAs
  • Small Molecule Libraries
  • Silicon Dioxide