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Volume 4 Nano Research & Applications
ISSN: 2471-9838
Page 65
JOINT EVENT
August 16-18, 2018 | Dublin, Ireland
&
12th Edition of International Conference on
Nanopharmaceutics and Advanced Drug Delivery
25th Nano Congress for Future Advancements
Nano Congress 2018
&
Nano Drug Delivery 2018
August 16-18, 2018
Anticancer activity of G rich aptamer AS1411 grafted to gold nanospheres: From synthesis to
mechanism study
Samaneh Kabirian Dehkordi1,2,4, Mounira Chalabi Dchar1, Karine Monier1 , Hichem Mertani4, Jean Jacques Diaz1,4, Masoud A Mehrgardi2 and Philippe
Bouvet1,3
1CRCL, France
2University of Isfahan, Iran
3ENS de Lyon, France
4UCBL1, France
AS1411 is a G-rich oligodeoxynucleotide aptamer that has been used in phase II clinical trials for the potential treatment of
cancers. Forming a G-quartet structure, AS1411 binds to cell surface nucleolin specifically, and is subsequently internalized
into the tumor cell. It remains unclear how AS1411 binding to nucleolin leads to cell proliferation inhibition and cell death.
Despite remarkable AS1411 results in a few patients, the overall rate of response has been low, possibly because it has less
than optimal pharmacology and relatively low potency. Attaching AS1411 to gold nanospheres (AS1411-GNSs) increases its
accumulation in cancer cells and enhances its antitumor efficacy by binding to cellular nucleolin. Nucleolin is associated with
ribosomal DNA (rDNA) and is absolutely required for rRNA synthesis. It binds with nanomolar affinities the G-quadruplex
rDNA sequences to increase the rate of RNA polymerase I (POL1) transcription. We developed a new complex of AS1411
conjugated to Gold nanospheres (GACGs). This complex was more stable and effective than AS1411 in treated tumor cell lines.
GACGs decrease nucleolin expression affecting tumor cell proliferation and POLI targeting genes transcription such as 5’ETS
and 18s. Thus, GACGs targeting Nucleolin/rDNA complexes inhibit POLI and represents a novel, nucleolar targeting approach
to selectively disrupt proliferation in cancer cells and induce cell death.
Recent Publications
1. Motaghi H, Mehrgardi M A and Bouvet P (2017) Carbon dots-AS1411 aptamer nanoconjugate for ultrasensitive
spectrofluorometric detection of cancer cells. Sci Rep. 7:10513.
2. Kumar S et al. (2017) Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of
nucleolin. Sci Rep. 7(1):9017.
3. Ugrinova I et al. (2018) Multifaceted nucleolin protein and its molecular partners in oncogenesis. Adv. Protein Chem.
Struct. Biol. 111:133-164.
4. Bouvet P (2015) Identification of Nucleic Acid High Affinity Binding Sequences of Proteins by SELEX. In Methods in
Molecular Biology. 1334:333-43.
5. Khoshfetrat S M and Mehrgardi M A (2017) Amplified detection of leukemia cancer cells using an aptamer-conjugated
gold-coated magnetic nanoparticles on a nitrogen-doped graphene modified electrode. Bioelectrochemistry. 114:24-32.
Biography
Samaneh Kabirian, a Chemist completed her Bachelor’s Degree in Pure Chemistry; Master’s Degree in Analytical Chemistry (detection of biomolecule in blood).
She has her expertise in synthesis, characterization of nanoparticles conjugated to aptamers and passion in improving its application in biology of cancer. She
is always curious and enthusiastic to work on multidisciplinary project and bridging gap between different domains of science. She is currently pursuing a double
degree PhD in Molecular and Cellular Biology at the University of Lyon (France) and in Analytical Chemistry at Isfahan University (Iran). She has been studying
and working in biochemistry and biology laboratory of cancer research center of Lyon (France) for the past 3 years. She gave her a good point of view to biological
aspects of applications of nanoparticles in biology of cancer. With strong background in chemistry and specially analytical chemistry, she is also trained in all
common molecular and cellular biology manipulations like cell culture, protein and DNA analysis and so on. Her double skilled ability helps build a good connection
in multidisciplinary project especially cancer biology and pharmaceutical chemistry.
Samaneh Kabirian Dehkordi et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-015