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

Peng Mi, Daisuke Kokuryo, Horacio Cabral, Michiaki Kumagai, Takahiro Nomoto, Ichio Aoki, Yasuko Terada, Akihiro Kishimura, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticle

77 Citations (Scopus)

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 80 nm, 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.

Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalJournal of Controlled Release
Volume174
Issue number1
DOIs
Publication statusPublished - Jan 28 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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