Nanoformulated cell-penetrating survivin mutant and its dual actions

Bhasker Sriramoju, Rupinder K Kanwar, Jagat R Kanwar Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine, Faculty of Health, Deakin University, Geelong, Australia Abstract: In this study, we investigated the differential actions of a dominant-negat...

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Autores principales:	Sriramoju B, Kanwar RK, Kanwar JR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0a1a3526d437406d81b5839afe1078d1
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spelling	oai:doaj.org-article:0a1a3526d437406d81b5839afe1078d12021-12-02T00:46:39ZNanoformulated cell-penetrating survivin mutant and its dual actions1178-2013https://doaj.org/article/0a1a3526d437406d81b5839afe1078d12014-07-01T00:00:00Zhttp://www.dovepress.com/nanoformulated-cell-penetrating-survivin-mutant-and-its-dual-actions-a17536https://doaj.org/toc/1178-2013 Bhasker Sriramoju, Rupinder K Kanwar, Jagat R Kanwar Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine, Faculty of Health, Deakin University, Geelong, Australia Abstract: 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. Keywords: survivin mutant, neurological disorders, protein therapeutics, inhibitor of apoptosis protein family, poly(lactic-co-glycolic acid)Sriramoju BKanwar RKKanwar JRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3279-3298 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Sriramoju B Kanwar RK Kanwar JR Nanoformulated cell-penetrating survivin mutant and its dual actions
description	Bhasker Sriramoju, Rupinder K Kanwar, Jagat R Kanwar Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine, Faculty of Health, Deakin University, Geelong, Australia Abstract: 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. Keywords: survivin mutant, neurological disorders, protein therapeutics, inhibitor of apoptosis protein family, poly(lactic-co-glycolic acid)
format	article
author	Sriramoju B Kanwar RK Kanwar JR
author_facet	Sriramoju B Kanwar RK Kanwar JR
author_sort	Sriramoju B
title	Nanoformulated cell-penetrating survivin mutant and its dual actions
title_short	Nanoformulated cell-penetrating survivin mutant and its dual actions
title_full	Nanoformulated cell-penetrating survivin mutant and its dual actions
title_fullStr	Nanoformulated cell-penetrating survivin mutant and its dual actions
title_full_unstemmed	Nanoformulated cell-penetrating survivin mutant and its dual actions
title_sort	nanoformulated cell-penetrating survivin mutant and its dual actions
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/0a1a3526d437406d81b5839afe1078d1
work_keys_str_mv	AT sriramojub nanoformulatedcellpenetratingsurvivinmutantanditsdualactions AT kanwarrk nanoformulatedcellpenetratingsurvivinmutantanditsdualactions AT kanwarjr nanoformulatedcellpenetratingsurvivinmutantanditsdualactions
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Nanoformulated cell-penetrating survivin mutant and its dual actions

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