Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors

J Control Release. 2014 Jan 28:174:63-71. doi: 10.1016/j.jconrel.2013.10.038. Epub 2013 Nov 6.

Abstract

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis.

Keywords: Block copolymer; Calcium phosphate nanoparticles; Cancer diagnosis; Gd-DTPA; Hydrothermal synthesis; MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Calcium Phosphates / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Contrast Media / pharmacology
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Drug Carriers / pharmacology
  • Female
  • Gadolinium DTPA / chemistry*
  • Gadolinium DTPA / pharmacokinetics
  • Gadolinium DTPA / pharmacology
  • Hot Temperature
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Neoplasms / diagnosis
  • Neoplasms / metabolism
  • Polyethylene Glycols / chemistry*

Substances

  • Calcium Phosphates
  • Contrast Media
  • Drug Carriers
  • Polyethylene Glycols
  • calcium phosphate
  • Gadolinium DTPA