Bioimaging of hyaluronic acid derivatives using nanosized carbon dots

Biomacromolecules. 2012 Aug 13;13(8):2554-61. doi: 10.1021/bm300796q. Epub 2012 Jul 30.

Abstract

Fluorescent nanosized carbon dots (Cdots) are an emerging bioimaging agent with excellent chemical inertness and marginal cytotoxicity in comparison to widely used semiconductor quantum dots. In this work, we report the application of Cdots for real time bioimaging of target specific delivery of hyaluronic acid (HA) derivatives. Polyethylene glycol (PEG) diamine-capped Cdots were synthesized by the pyrolysis of citric acid in a hot solvent. The synthesized Cdots showed strong fluorescence under UV excitation with emission properties dependending on the excitation wavelength. HA-Cdot conjugates were synthesized by amide bond formation between amine groups of Cdot and carboxylic groups of HA. After confirmation of the negligible cytotoxicity of Cdots and HA-Cdot conjugates, in vitro bioimaging was carried out for target specific intracellular delivery of the HA-Cdot conjugates by HA receptor-mediated endocytosis. Furthermore, in vivo real-time bioimaging of Cdots and HA-Cdot conjugates exhibited the target specific delivery of HA-Cdot conjugates to the liver with abundant HA receptors. Taken together, we could confirm the feasibility of HA derivatives as a target-specific drug delivery carrier for the treatment of liver diseases and Cdots as a promising bioimaging agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / chemistry*
  • Cell Survival / drug effects
  • Diamines / chemistry
  • Drug Carriers
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / pharmacokinetics
  • Fluorescent Dyes / toxicity
  • HEK293 Cells
  • Humans
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / chemistry*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Atomic Force
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Optical Imaging*
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Tissue Distribution

Substances

  • Diamines
  • Drug Carriers
  • Fluorescent Dyes
  • Polyethylene Glycols
  • Carbon
  • Hyaluronic Acid