TY - JOUR
T1 - 99mTc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of ανβ3-mediated tumor expression and feasibility for hyperthermia treatment
AU - Tsiapa, Irene
AU - Efthimiadou, Eleni K.
AU - Fragogeorgi, Eirini
AU - Loudos, George
AU - Varvarigou, Alexandra D.
AU - Bouziotis, Penelope
AU - Kordas, George C.
AU - Mihailidis, Dimitris
AU - Nikiforidis, George C.
AU - Xanthopoulos, Stavros
AU - Psimadas, Dimitrios
AU - Paravatou-Petsotas, Maria
AU - Palamaris, Lazaros
AU - Hazle, John D.
AU - Kagadis, George C.
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Hypothesis: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted 99mTc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. Experiments: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανβ3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. Findings: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted 99mTc-NPs poorly internalized in the tumor, while the targeted 99mTc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.
AB - Hypothesis: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted 99mTc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. Experiments: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανβ3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. Findings: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted 99mTc-NPs poorly internalized in the tumor, while the targeted 99mTc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.
KW - Hyperthermia
KW - Integrin
KW - Nanoparticles
KW - RGD
KW - Radiolabeling
KW - Technetium
UR - http://www.scopus.com/inward/record.url?scp=84910046689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84910046689&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2014.07.032
DO - 10.1016/j.jcis.2014.07.032
M3 - Article
C2 - 25128864
AN - SCOPUS:84910046689
SN - 0021-9797
VL - 433
SP - 163
EP - 175
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -