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Literature & Humanities
http://ijpt.iums.ac.ir
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admin
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8888
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jalali
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gregorian
2018
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On-demand cellular uptake of cysteine conjugated gadolinium based mesoporous silica nanoparticle with breast cancer-cells
Chemotherapy, Antibiotics and Gene Therapy
پژوهشي
Research Article
<div style="text-align: justify;">Design, synthesis, and conjugation of mesoporous silica nanoparticles (MSNs) with biomolecules is a matter of growing interest to enhance selective uptake of contrast agents like gadolinium (Gd3+) by cancer cells. Here, by targeting xc-cystine/glutamate antiporter system in breast cancer cells, conjugation of MSN-Gd3+ with cysteine is used to enhance cancer cellular uptake of Gd3+. Reactions designed to make different covalent bonds between MSNs and cysteine to investigate impact of cysteine conjugation of MSNs-Gd3+ on uptake of Gd3+ by breast cancer cells. Cysteine amino acids were attached to the surface of MSNs via its three functional groups using three different conjugation methods. Therefore, the external surface of MSNs were first modified by three different linkers to create amine, epoxy, and isocyanate groups on the surface of MSNs, then pores loaded with Gd3+ complexes and reacted with toile, epoxy, and amine groups of cysteine, respectively (nanoprobe A, B and C). The nanoprobes were characterized using different techniques, including (scanning electron microscope) SEM, Brunauer–Emmett–Teller BET, dynamic light scattering (DLS) and Fourier Transform Infrared (FTIR). The intracellular uptake of nanoprobes by human dermal fibroblasts (HDF) and human breast adenocarcinoma cells (MCF-7) was investigated using inductively coupled plasma atomic emission spectrometer (ICP-AES). Results demonstrated that accumulation of Gd3+ in cancer cells is highly related to method of cysteine conjugation. The amount of Gd3+ was taken by cancer cells increased 7 folds, when thiol group of cysteine was responsible to make covalent bond with MSNs, in other words when the zwitterionic form of cysteine was on the surface (nanoprobe B). The average intracellular uptake of Gd3+ by cancer cells was 0.5±0.09 pg/cell. On the other hand, uptake of Gd3+ delivered by nanoprobe B into cancer cells was up to 4.7 times higher than normal cells. No appreciable cytotoxicity was seen using HDF and MCF-7 cell lines. This study provides MRI nanoprobes using suitable conjugation of Gd3+ based MSNs with cysteine for next studies about MR imaging of cancer.</div>
Breast Cancer, Cysteine, Gadolinium, Mesoporous Silica Nanoparticle
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http://ijpt.iums.ac.ir/browse.php?a_code=A-10-52-1&slc_lang=en&sid=1
HOJJATOLLAH
NAZARI
10031947532846001590
10031947532846001590
No
Department of Medical Nanotechnology, Faculty of Advanced Technology in Medicine, Iran University of Medical Sciences, Tehran, Iran
KHADIJEH
ASHTARI
10031947532846001591
10031947532846001591
No
Stem Cell Technology Center, Tehran, Iran
MASOUD
SOLEIMANI
10031947532846001592
10031947532846001592
No
Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
KOWSAR
BAGHERZADEH
10031947532846001593
10031947532846001593
No
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
SEPIDEH
SAFARI
10031947532846001594
10031947532846001594
No
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
BITA
MEHRAVI
10031947532846001595
10031947532846001595
Yes
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran