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Locked nucleic acid modified bi-specific aptamer-targeted nanoparticles carrying survivin antagonist towards effective colon cancer therapy

Roy, Kislay, Kanwar, Rupinder K., Cheung, Chun Hei Antonio, Fleming, Cassandra Lee, Veedu, Rakesh N., Krishnakumar, Subramanian and Kanwar, Jagat R. 2015, Locked nucleic acid modified bi-specific aptamer-targeted nanoparticles carrying survivin antagonist towards effective colon cancer therapy, RSC advances, vol. 5, no. 37, pp. 29008-29016, doi: 10.1039/c5ra03791c.

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Title Locked nucleic acid modified bi-specific aptamer-targeted nanoparticles carrying survivin antagonist towards effective colon cancer therapy
Author(s) Roy, Kislay
Kanwar, Rupinder K.
Cheung, Chun Hei Antonio
Fleming, Cassandra Lee
Veedu, Rakesh N.
Krishnakumar, Subramanian
Kanwar, Jagat R.
Journal name RSC advances
Volume number 5
Issue number 37
Start page 29008
End page 29016
Total pages 9
Publisher Royal Society of Chemistry
Place of publication Cambridge, Eng.
Publication date 2015-01-01
ISSN 2046-2069
Keyword(s) Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
COLORECTAL-CANCER
DRUG-DELIVERY
STEM-CELLS
NUCLEOLIN
CHITOSAN
EPCAM
EXPRESSION
APOPTOSIS
SURFACE
ABSORPTION
Summary We investigated the anti-cancer activity of alginate coated chitosan nanoparticles (CHNP) encapsulating cell-permeable dominant negative survivin (SR9) with locked nucleic acid (LNA) aptamers targeting EpCAM and nucleolin (termed as "nanobullets") in vitro (2D and 3D cell culture models) and in vivo (colon cancer mouse xenograft model). We incorporated three LNA modifications in each sequence in order to enhance the stability of these aptamers. Confocal microscopy revealed binding of the LNA-aptamers to their specific markers with high affinity. The muco-adhesive nanobullets showed 6-fold higher internalization in cancer cells when compared to non-cancerous cells, suggesting a tumour specific uptake. A higher intensity of nanobullets was observed in both the periphery and the core of the multicellular tumour spheroids compared to non-targeted CHNP-SR9. The nanobullets were found to be the highly effective as they led to a 2.26 fold (p < 0.05) reduction at 24 h and a 4.95 fold reduction (p ≤ 0.001) in the spheroid size at 72 h. The tumour regression was 4 fold higher in mice fed on a nanobullet diet when compared to a control diet. The nanobullets were able to show a significantly high apoptotic (p ≤ 0.0005) and necrotic index in the tumour cell population (p ≤ 0.005) when compared to void NPs. Therefore, our nanoparticles have shown highly promising results and therefore deliver a new conduit towards the approach of cancer-targeted nanodelivery. This journal is
Language eng
DOI 10.1039/c5ra03791c
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Royal Society of Chemistry
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075690

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