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. Attached Files Name Description MIMEType Size Downloads sriramoju-nanoformulated-2014.pdf Published version application/pdf 9.55MB 172 Title Nanoformulated cell-penetrating survivin mutant and its dual actions Author(s) Sriramoju, Bhasker Kanwar, Rupinder K. Kanwar, Jagat R. orcid.org/0000-0003-3728-9568 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 Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30067298 Document type: Journal Article Collections: Faculty of Health School of Medicine Institute for Frontier Materials Open Access Collection GTP Research Related Links Link Description Connect to Elements publication management system Go to link with your DU access privileges   Connect to published version Go to link with your DU access privileges   Author URL Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. 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. Versions Version Filter Type Tue, 11 Nov 2014, 10:55:58 EST Tue, 09 Dec 2014, 09:44:13 EST Tue, 09 Dec 2014, 13:21:41 EST Tue, 09 Dec 2014, 13:41:08 EST Tue, 16 Dec 2014, 14:11:39 EST Tue, 16 Dec 2014, 14:12:55 EST Thu, 18 Dec 2014, 10:40:16 EST Fri, 06 Feb 2015, 11:32:14 EST Wed, 14 Oct 2015, 13:55:54 EST Wed, 07 Sep 2016, 07:55:51 EST Wed, 06 Dec 2017, 06:10:30 EST Fri, 07 Sep 2018, 17:20:46 EST Filtered Full Citation counts:   Cited 15 times in TR Web of Science Cited 15 times in Scopus Search Google Scholar Access Statistics: 944 Abstract Views, 173 File Downloads  -  Detailed Statistics Created: Tue, 09 Dec 2014, 09:44:13 EST