ABSTRACT
Methionine-gold nanoparticles (MGNs) was synthesized by conjugating methionine via dithiocarbamate linkage to gold nanoparticles (GNPs), prepared simultaneously by one pot modified Burst method. Formation of MGNs was confirmed by UV-visible spectroscopy and appearance of new IR bands in the range of 934 cm-1 to 1086 cm-1 and shifting of N-C,S-S and S-C-S stretching, confirms the involvement of '-S-C-S-' group of methionine dithiocarbamate with GNPs. The presence of Au in MGNs was confirmed by EDXA spectrum, whereas TEM, SAED and XRD revealed that MGNs are nanocrystalline (~13 nm) and have face-centered cubic structure. MGNs was labeled with 99mTc (TMGNs) with radiolabeling efficiency greater than 99% using 300 µg of stannous chloride, pH 7 and 90.6 MBq of 99mTcO4. The stability data showed that the conjugate will remain infrangible in systemic circulation and in acidic microenvironment of tumor. The blood kinetic profile of TMGN in rabbits and biodistribution studies in EAT tumor bearing balb/c mice showed longer in vivo circulation and slow clearance compared to radiolabeled methionine (TM). TMGN demonstrated nearly three-fold higher tumor accumulation (3.9 ± 0.35% ID/g), 2-fold lower tumor saturation dose (1.0 µg/kg) and higher tumor retention compared with TM. Data showed that the TMGN tumor: blood ratio (1.05) is nearly 2.5-fold higher than TM (0.44), whereas TMGN tumor: muscle ratio (97.5) is nearly 8-fold higher than TM (11.6). In conclusion, TMGN showed excellent tumor targeting and has promising prospects as a SPECT-radiopharmaceutical for imaging tumors.
Subject(s)
Gold , Metal Nanoparticles , Animals , Biocompatible Materials , Cell Line, Tumor , Methionine , Mice , Rabbits , Technetium , Tissue DistributionABSTRACT
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 dextranto 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 99mTc show the enhanced uptake at the tumor site showing its enhanced specificity.
Subject(s)
Dextrans/chemistry , Ferric Compounds/chemistry , Folic Acid/pharmacology , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles/chemistry , Nanoparticles/chemistry , Radionuclide Imaging/methods , Animals , Cell Death/drug effects , Cell Line , Cell Survival/drug effects , Humans , Magnetic Resonance Spectroscopy , Magnetometry , Mice , Mice, Inbred BALB C , Nanoparticles/ultrastructure , Neoplasms/diagnostic imaging , Neoplasms/pathology , Particle Size , Phantoms, Imaging , Rabbits , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Static Electricity , Tissue Distribution/drug effects , Vibration , X-Ray DiffractionABSTRACT
In this paper, we have proposed a simple method to covalently conjugate biotin to magnetic nanoparticles, which can be targeted to the tumour sites by using pretargeting approach with avidin or streptavidin. Magnetic nanoparticles of manganese ferrite were synthesized by alkaline coprecipitation of ferric chloride hexahydrate, ferrous sulphate heptahydrate and manganese sulphate monohydrate using ammonium hydroxide. The synthesized magnetic nanoparticles were then successfully surface modified by using 3-aminopropyl trimethoxysilane, and the amount of aminopropylsilane bound to the surface of magnetic nanoparticles was quantified by measuring the absorbance of a purple-coloured complex (Ruhemann's purple) formed between amine group and ninhydrin at 576 nm. The aminated magnetic nanoparticles were then conjugated to biotin by reacting them with N-hydroxysuccinimide-biotin in dimethylsulphoxide. The successful conjugation of biotin to magnetic nanoparticles was confirmed by Fourier transform infrared spectroscopy. The size, phase and magnetic nature of the synthesized nanoparticles were analysed by using various techniques like transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy and vibrating sample magnetometry.
