Design, preparation, and in vitro characterization of a trimodally-targeted nanomagnetic onco-theranostic system for cancer diagnosis and therapy (original) (raw)
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The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8-10 nm), and relatively high T 2 relaxivity (R 2 = 222L ⋅ mmol −1 ⋅ sec −l ). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T 2 -weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer.
2005
ABSTRACT Folic acid (FA) was conjugated to superparamagnetic iron oxide nanoparticles to develop a tumor specific contrast agent for magnetic resonance imaging (MRI). In this scheme a bifunctional poly (ethylene glycol)(PEG) linker was utilized to both increase biocompatibility and reduce nanoparticle agglomeration. The uptake of nanoparticle-PEG-FA conjugates by folate-receptor (FR) positive MCF-7 cells was compared against that of nanoparticles coated with only PEG over a range cell incubation times.
International Journal of Nanomedicine, 2012
The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8-10 nm), and relatively high T 2 relaxivity (R 2 = 222L ⋅ mmol −1 ⋅ sec −l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T 2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer.
MR imaging and targeting of human breast cancer cells with folate decorated nanoparticles
The way of viewing cancer has advanced considerably in the last few decades because of recent progress on two different topics: the knowledge of the mechanisms and characteristics of cancer and the innovation in imaging agent design. In particular the unique properties of cancer that allow differentiation from normal tissue could be employed in multi-functional nanoparticle imaging development. Genetic alterations, either endogenous or induced through gene therapy, are one class of such characteristics. At the same time proteomic differences such as overexpressed surface receptors are another targetable feature, used for enhanced nanoparticle retention. The here proposed magnetic nanoparticle (with biocompatible coating) was designed to target the human breast MDA-MB-231 tumor induced on a nude mice model. With the aim of developing a theranostic agent, the overexpression of folate protein receptor in breast cancer cells was exploited, decorating with folate an organic nanocarrier loaded with magnetite nanoparticles that acts as a diagnostic MRI (Magnetic Resonance Imaging) contrast agent, and Paclitaxel (PTX) as antitumoral drug. A high uptake of nanoparticles and remarkable effect on in vivo MRI images show the targeting ability of our compound and its prolonged retention in tumor tissues. Due to the presence of PTX, the developed nanocarrier may potentially be used also for therapeutic purposes. † Electronic supplementary information (ESI) available: The details of the nanoparticle characterization not specied in Materials and Methods (AFM image of Block-MNP-FA and NMRD relaxivity curves of NPs) are reported in ESI. See
Scientific Reports
Folate-targeted iron oxide nanoparticles (FA@Fe3O4 NPs) were prepared by a one-pot hydrothermal method and then used as cancer theranostic agents by combining magnetic resonance imaging (MRI) and magnetic hyperthermia therapy (MHT). Crystal structure, morphology, magnetic properties, surface functional group, and heating efficacy of the synthesized nanoparticles were characterized by XRD, TEM, VSM, FTIR, and hyperthermia analyses. The results indicated that the crystal structure, magnetic properties, and heating efficacy of the magnetite nanoparticles were improved by hydrothermal treatment. Toxicity of the prepared NPs was assessed in vitro and in vivo on the mammary cells and BALB/c mice, respectively. The results of the in vitro toxicity analysis showed that the FA@Fe3O4 NPs are relatively safe even at high concentrations of the NPs up to 1000 µg mL−1. Also, the targetability of the FA@Fe3O4 NPs for the detection of folate over-expressed cancer cells was evaluated in an animal mo...
Background: Advances of nanotechnology have led to the development of nano-materials with both potential diagnostic and therapeutic applications. Among them, Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) have received particular attention. Modified EDC coupling fraction was used to fabricate the SPION-C595 as an MR imaging contrast agent for breast cancer detection in early stages. Methods: Nanoprobe characterization was confirmed using Fourier Transform Infra-red Spectroscopy (FT-IR), Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy (SEM-EDAX), and Photon Correlation Spectroscopy (PCS). Protein and iron concentration of nanoprobe was examined by standard method. MTT assay was performed to evaluate the cytotoxicity of the nanoprobe in breast cancer cell line (MCF-7). T 2-weighted MR imaging was performed to evaluate the signal enhancement on T 2 relaxation time of nanoprobe using spin-echo pulse sequence. Results: As results showed, SPIONs-C595 provided active targeting of breast cancer cell (MCF-7) at a final concentration of 600 μgFe/ml. The final concentration of protein was calculated to be at 0.78 μgprotein/ml. The hydrodynamic size of the nano-probe was 87.4±0.7 nm. The MR imaging results showed a good reduction of T 2 relaxation rates for the highest dose of SPIONs-C595. Discussion: Based on the results, SPIONs-C595 nanoprobe has a potential in T 2-weighted MR imaging contrast agent for breast cancer cell (MCF-7) detection.
Molecules
In recent years, the intrinsic magnetic properties of magnetic nanoparticles (MNPs) have made them one of the most promising candidates for magnetic resonance imaging (MRI). This study aims to evaluate the effect of different coating agents (with and without targeting agents) on the magnetic property of MNPs. In detail, iron oxide nanoparticles (IONPs) were prepared by the polyol method. The nanoparticles were then divided into two groups, one of which was coated with silica (SiO2) and hyperbranched polyglycerol (HPG) (SPION@SiO2@HPG); the other was covered by HPG alone (SPION@HPG). In the following section, folic acid (FA), as a targeting agent, was attached on the surface of nanoparticles. Physicochemical properties of nanostructures were characterized using Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and a vibrating sample magnetometer (VSM). TEM results showed that SPION@HPG was monodispersed with the average size of about 20 nm, whil...
Biomacromolecules, 2017
The low therapeutic index of conventional chemotherapy and poor prognosis of patients diagnosed with metastatic cancers are prompting clinicians to adopt newer strategies to simultaneously detect cancer lesions at an early stage and to precisely deliver anticancer drugs to tumor sites. In this study, we employed a novel strategy to engineer a polyvalent theranostic nanocarrier consisting of superparamagnetic iron oxide nanoparticle core (SPIONs) decorated with folic acid-polyamidoamine dendrimers surface (FA-PAMAM). In addition, a highly potent hydrophobic anticancer agent 3,4-difluorobenzylidene-curcumin (CDF) was coloaded in the FA-PAMAM dendrimer to increase its solubility and assess its therapeutic potentials. The resulting targeted nanoparticles (SPIONs@FA-PAMAM-CDF) exhibited high MR contrast. When tested on folate receptor overexpressing ovarian (SKOV3) and cervical (HeLa) cancer cells, the CDF loaded targeted nanoformulations showed higher accumulation with a better anticanc...
Journal of Biomedical Nanotechnology, 2013
The physical and chemical properties of the nanoparticles influence their pharmacokinetics and ability to accumulate in tumors. In this paper we report a facile method to conjugate folic acid molecule to iron oxide nanoparticles to increase the specific uptake of these nanoparticles by the tumor, which will be useful in targeted imaging of the tumor. The iron oxide nanoparticles were synthesized by alkaline co precipitation method and were surface modified with dextran to make them stable. The folic acid is conjugated to the dextran modified iron oxide nanoparticles by reductive amination process after the oxidation of the dextran with periodate. The synthesized folic acid conjugated nanoparticles were characterized for size, phase, morphology and magnetization by using various physicochemical characterization techniques such as transmission electron microscopy, X-ray diffraction, fourier transform infrared spectroscopy, vibrating sample magnetometry, dynamic light scattering and zetasizer etc. The quantification of the generated carbonyl groups and folic acid conjugated to the surface of the magnetic nanoparticles was done by colorimetric estimations using UV-Visible spectroscopy. The in vitro MR studies were carried out over a range of concentrations and showed significant shortening of the transverse relaxation rate, showing the ability of the nanoconjugate to act as an efficient probe for MR imaging. The biodistribution studies and the scintigraphy done by radiolabeling the nanoconjugate with 99m Tc show the enhanced uptake at the tumor site showing its enhanced specificity.
International journal of biological macromolecules, 2016
Target-specific MRI contrast agent based on super-paramagnetic iron oxide-chitosan-folic acid (SPIONP-CS-FA) nanoparticles was fabricated by using an ionotropic gelation method, which involved the loading of SPIONPs at various concentrations into CS-FA nanoparticles by electrostatic interaction. The SPIONP-CS-FA nanoparticles were characterized by ATR-FTIR, XRD, TEM, and VSM techniques. This study revealed that the advantages of this system would be green fabrication, low cytotoxicity at iron concentrations ranging from 0.52mg/L to 4.16mg/L, and high water stability (pH 6) at 4°C over long periods. Average particle size and positive zeta-potential of the SPIONP-CS-FA nanoparticles was found to be 130nm with narrow size distribution and 42mV, respectively. In comparison to SPIONP-0.5-CS nanoparticles, SPIONP-0.5-CS-FA nanoparticles showed higher and specific cellular uptake levels into human cervical adenocarcinoma cells due to the presence of folate receptors, while in vivo results ...