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Nanoformulated cell-penetrating survivin mutant and its dual actions

Sriramoju, Bhasker, Kanwar, Rupinder K. and Kanwar, Jagat R. 2014, Nanoformulated cell-penetrating survivin mutant and its dual actions, International journal of nanomedicine, vol. 9, no. 1, pp. 3279-3298, doi: 10.2147/IJN.S60169.

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Title Nanoformulated cell-penetrating survivin mutant and its dual actions
Author(s) Sriramoju, Bhasker
Kanwar, Rupinder K.
Kanwar, Jagat R.
Journal name International journal of nanomedicine
Volume number 9
Issue number 1
Start page 3279
End page 3298
Total pages 20
Publisher Dove Medical Press
Place of publication Auckland, New Zealand
Publication date 2014-07-10
ISSN 1176-9114
1178-2013
Keyword(s) inhibitor of apoptosis protein family
neurological disorders
poly(lactic-co-glycolic acid)
protein therapeutics
survivin mutant
Science & Technology
Life Sciences & Biomedicine
Nanoscience & Nanotechnology
Pharmacology & Pharmacy
Science & Technology - Other Topics
LOADED PLGA NANOPARTICLES
IN-VITRO EVALUATION
AUTOIMMUNE ENCEPHALOMYELITIS
CASPASE ACTIVATION
CEREBRAL-ISCHEMIA
CYTOCHROME-C
CYCLIN D1
APOPTOSIS
PROTEIN
EXPRESSION
Summary In this study, we investigated the differential actions of a dominant-negative survivin mutant (SurR9-C84A) against cancerous SK-N-SH neuroblastoma cell lines and differentiated SK-N-SH neurons. In both the cases, the mutant protein displayed dual actions, where its effects were cytotoxic toward cancerous cells and proliferative toward the differentiated neurons. This can be explained by the fact that tumorous (undifferentiated SK-N-SH) cells have a high endogenous survivin pool and upon treatment with mutant SuR9-C84A causes forceful survivin expression. These events significantly lowered the microtubule dynamics and stability, eventually leading to apoptosis. In the case of differentiated SK-N-SH neurons that express negligible levels of wild-type survivin, the mutant indistinguishably behaved in a wild-type fashion. It also favored cell-cycle progression, forming the chromosome-passenger complex, and stabilized the microtubule-organizing center. Therefore, mutant SurR9-C84A represents a novel therapeutic with its dual actions (cytotoxic toward tumor cells and protective and proliferative toward neuronal cells), and hence finds potential applications against a variety of neurological disorders. In this study, we also developed a novel poly(lactic-co-glycolic acid) nanoparticulate formulation to surmount the hurdles associated with the delivery of SurR9-C84A, thus enhancing its effective therapeutic outcome.
Language eng
DOI 10.2147/IJN.S60169
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Dove Medical Press
Persistent URL http://hdl.handle.net/10536/DRO/DU:30067298

Document type: Journal Article
Collections: School of Medicine
Institute for Frontier Materials
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.