TY - JOUR
T1 - Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors
AU - Mi, Peng
AU - Kokuryo, Daisuke
AU - Cabral, Horacio
AU - Kumagai, Michiaki
AU - Nomoto, Takahiro
AU - Aoki, Ichio
AU - Terada, Yasuko
AU - Kishimura, Akihiro
AU - Nishiyama, Nobuhiro
AU - Kataoka, Kazunori
N1 - Funding Information:
This research was financially supported by Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST) from the Japan Society for the Promotion of Science (JSPS) (K.K.) and Takeda Science Foundation (N.N.). P.M. thanks the support of a JSPS fellowship. TEM measurements were conducted in Research Hub for Advanced Nano Characterization, The University of Tokyo, supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. μ-SR-XRF characterizations were supported by the Nanotechnology Support Program of the Japan Synchrotron Radiation Research Institute (JASRI). We thank Ms. Sayaka Shibata and Ms. Aiko Sekita (NIRS) for technical support.
PY - 2014/1/28
Y1 - 2014/1/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888590878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888590878&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2013.10.038
DO - 10.1016/j.jconrel.2013.10.038
M3 - Article
C2 - 24211705
AN - SCOPUS:84888590878
SN - 0168-3659
VL - 174
SP - 63
EP - 71
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -
