Tryptophan conjugated magnetic nanoparticles for targeting tumors overexpressing indoleamine 2,3 dioxygenase (IDO) and L
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DELIVERY SYSTEMS Original Research
Tryptophan conjugated magnetic nanoparticles for targeting tumors overexpressing indoleamine 2,3 dioxygenase (IDO) and L-type amino acid transporter Rashi Mathur1 Ram Prakash Chauhan1,2 Gurjaspreet Singh3 Sweta Singh1 Raunak Varshney1 Ankur Kaul1 Sanyog Jain4 Anil Kumar Mishra1 ●
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Abstract Tryptophan is an amino acid required by all life forms for protein synthesis and other important metabolic functions. It is metabolized in the body using the kynurenine pathway which involves the enzyme indoleamine 2,3 dioxygenase (IDO) and its transport is regulated through the L-type amino acid transporters (LAT 1). IDO and LAT 1 are found to be overexpressed in many cancers i.e., ovarian, lung colorectal etc. In this study we have used this specific interaction as the basis for designing diagnostic agent based on iron oxide nanoparticles which can specifically target the IDO/LAT 1 over expressing tumors. We have conjugated tryptophan to the surface of super-paramagnetic nanoparticles chemically using 3aminopropyltrimethoxysilane as a linker. The synthesized tryptophan conjugated magnetic nano-conjugate has been characterized using FTIR, UV–Vis, TEM for its shape size, charge and NMR and Mass for conjugation. The magnetization studies show decrease in the magnetic behavior after conjugation however the desired super-paramagnetic property is still retained as shown by the signature sigmoidal B-H curve. The nano-conjugate shows minimal cytotoxicity over 24 h as shown by the SRB assay in two cell lines A-549, MCF-7. Using 99mTc labeling the biodistribution and the blood kinetics of the magnetic nano-conjugate was evaluated. The study highlights the suitability of the designed magnetic Nano bioconjugate as a potential bimodal diagnostic agent. Graphical Abstract 120
y = 156.05x + 11.002 R² = 0.9719
R2 = 1/T2 (sec -1)
100 80 60 40 20 0 0 Iron Oxide
0.1
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Concentration (mMol)
Target
LAT-1 & IDO Overexpressing Tumors
LAT-1 & IDO Overexpressing Tumors d) 40
σs = 32.9 emu/g
30 20
B (emu/g)
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Received: 19 January 2020 / Accepted: 24 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
σs = 26.6 emu/g
10 0 -10 -20 -30 -40 -2000
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H (Oe)
99m
MNP
Tryptophan (Trp)
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Trp - MNPs
Supplementary information The online version of this article (https:// doi.org/10.1007/s10856-020-06438-x) contains supplementary material, which is available to authorized users. * Rashi Mathur [email protected]
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Department of Chemistry, Govt Post Graduate College, Bilas pur, Himacham Pradesh 174001, India
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Department of Chemistry, Panjab University, Chandigarh, India
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Department of Pharmaceutics, NIPER, Mohali, India
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S.K. Mazumdar Marg, Delhi 110054, India
87 Page 2 of 13
Journal of Materials Science: Ma
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