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.
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.
The design and surface chemistry of core shell quantum dots significantly affect their bio-distribution, kinetics and toxicity. Bis-ligands have been shown to improve the loading capacity and control the steric ligand packing density on the quantum dot surfaces, thus improving the biological properties and controlling the toxicity of the quantum dot nano-conjugates. In this study, we functionalized core shell CdSe:ZnS quantum dots with a homo-dimeric system (EDTA-Bis-Cysteamine) and evaluated their stability in vivo for diagnostic applications. This homo-dimeric N 2 S 2 system wraps the quantum dots and has pendant carboxylate moieties for further conjugation chemistry. The novelty in the system is that it can be loaded with a variety of metal atoms through dative bonds, even when the S atoms are attached to the ZnS shell. This results in the formation of a stable complex on a nano-platform for theranostic applications. The synthesized quantum dot nano-conjugate has been structurally evaluated using various analytical techniques.Spectrophotometric studies show the emission of the nano-conjugate at 530 nm, similar to the core shell. The haematology studies, biochemical assays and histopathology performed on the organs of interest showed no significant damage post injection over a time frame of 15 days. The generation of reactive oxygen species by the cadmium based quantum dot nano-conjugate has been evaluated for the first time in vivo using Ferric Reducing Antioxidant Power assay (FRAP). The pharmacokinetics and bio-distribution of the nano-conjugate has been studied using radiolabelling ( 99m Tc). After conjugation, the blood kinetics show increased availability of the quantum dots in the blood pool and the bio-distribution pattern also shows major changes. However, no significant toxic effects were observed during the time scale considered. This study highlights a facile route for designing small homo-dimeric ligand functionalized quantum dots nano-conjugates with favourable biological properties, enhancing their potential to be used as multi-modal imaging/theranostic agents.
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