Intracellular environment-responsive stabilization of polymer vesicles formed from head-tail type polycations composed of a polyamidoamine dendron and poly(L-lysine)

Molecules. 2013 Sep 30;18(10):12168-79. doi: 10.3390/molecules181012168.

Abstract

For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Cytoplasm / metabolism
  • Dendrimers / chemistry*
  • Dendrimers / toxicity
  • Disulfides / chemistry
  • Fluorescein / chemistry
  • Fluorescein / metabolism
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Glutathione / chemistry
  • HeLa Cells
  • Humans
  • Nanocapsules / chemistry*
  • Nanocapsules / toxicity
  • Oxidation-Reduction
  • Particle Size
  • Polylysine / chemistry*
  • Polylysine / toxicity
  • Rhodamines / chemistry
  • Rhodamines / metabolism

Substances

  • Dendrimers
  • Disulfides
  • Fluorescent Dyes
  • Nanocapsules
  • PAMAM Starburst
  • Rhodamines
  • rhodamine 6G
  • Polylysine
  • Glutathione
  • Fluorescein