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Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION-EGF) for targeting brain tumors.

ABSTRACT: Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION-EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION-EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION-EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION-EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION-EGF conjugates in animals provided receptor-mediated targeted delivery across the blood-brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P<0.001). SPION-EGF conjugates provide targeted delivery and efficient magnetic resonance contrast enhancement of EGFR-overexpressing C6 gliomas.

SUBMITTER: Shevtsov MA

PROVIDER: S-EPMC3888267 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION-EGF) for targeting brain tumors.

Shevtsov Maxim A MA Nikolaev Boris P BP Yakovleva Ludmila Y LY Marchenko Yaroslav Y YY Dobrodumov Anatolii V AV Mikhrina Anastasiya L AL Martynova Marina G MG Bystrova Olga A OA Yakovenko Igor V IV Ischenko Alexander M AM

International journal of nanomedicine 20140103

Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION-EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION-EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the ...[more]

PMID: 24421639

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Project description:Nanobubbles (NBs) are considered to be a new generation of ultrasound-responsive nanocarriers that can effectively target tumors, accurately release multi-drugs at desired locations, as well as simultaneously perform diagnosis and treatment. In this study, we designed theranostic NBs (FTY720@SPION/PFP/RGD-NBs) composed of RGD-modified liposomes as the shell, and perflenapent (PFP), superparamagnetic iron oxide nanoparticles (SPION), and fingolimod (2-amino-2[2-(4-octylphenyl)ethyl]-1,3-propanediol, FTY720) encapsulated as the core. The prepared FTY720@SPION/PFP/RGD-NBs were black spheres with a diameter range of 160-220 nm, eligible for enhanced permeability and retention (EPR) effects. The calculated average drug loading efficiency (LE) and encapsulation efficiency (EE) of the FTY720@SPION/PFP/RGD-NBs were 9.18 ± 0.61% and 88.26 ± 2.31%, respectively. With the promotion of low-intensity focused ultrasound (LIFU), the amount and the rate of FTY720 released from the prepared NB complex were enhanced when compared to the samples without LIFU treatment. In vitro magnetic resonance imaging (MRI) trials showed that the prepared FTY720@SPION/PFP/RGD-NBs had a high relaxation rate and MRI T2-weighted imaging (T2WI) scanning sensitivity conditions. The cell viability studies demonstrated that both HepG2 and Huh7 cells co-cultured with FTY720@SPION/PFP/RGD-NB (100 μg mL-1) + LIFU treatment had the lowest survival rate compared with the other groups at 24 h and 48 h, showing that FTY720@SPION/PFP/RGD-NB had the strongest anti-tumor efficiency among the prepared NBs. The cytotoxicity study also demonstrated that the prepared NBs had low toxicity to normal fibroblast 3T3 cells. Cellular uptake studies further indicated that both LIFU treatment and RGD modification could effectively improve the tumor-targeted effects, thereby enhancing the antitumor efficacy. The qRT-PCR results indicated that LIFU-mediated FTY720@SPION/PFP/RGD-NB could significantly cause the activation of Caspase3, Caspase9 and p53 compared to the control group, inducing HepG2 apoptosis. These results together indicated that FTY720@SPION/PFP/RGD-NBs combined with LIFU may serve as a multifunctional drug delivery platform for hepatocellular carcinoma treatment and provide a new strategy for tumor visualization by MRI.

Dataset Information

Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION-EGF) for targeting brain tumors.

Publications

Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION-EGF) for targeting brain tumors.

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