Targeted gene delivery in tumor xenografts by the combination of ultrasound-targeted microbubble destruction and polyethylenimine to inhibit survivin gene expression and induce apoptosisReportar como inadecuado




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Journal of Experimental and Clinical Cancer Research

, 29:152

First Online: 23 November 2010Received: 16 October 2010Accepted: 23 November 2010

Abstract

BackgroundNoninvasive and tissue-specific technologies of gene transfection would be valuable in clinical gene therapy. This present study was designed to determine whether it could enhance gene transfection in vivo by the combination of ultrasound-targeted microbubble destruction UTMD with polyethylenimine PEI in tumor xenografts, and illuminate the effects of gene silencing and apoptosis induction with short hairpin RNA shRNA interference therapy targeting human survivin by this novel technique.

MethodsTwo different expression vectors pCMV-LUC and pSIREN were incubated with PEI to prepare cationic complexes PEI-DNA and confirmed by the gel retardation assay. Human cervical carcinoma Hela tumors were planted subcutaneously in both flanks of nude mice. Tumor-bearing mice were administered by tail vein with PBS, plasmid, plasmid and SonoVue microbubble, PEI-DNA and SonoVue microbubble. One tumor was exposed to ultrasound irradiation, while the other served as control. The feasibility of targeted delivery and tissue specificity facilitated by UTMD and PEI were investigated. Moreover, immunohistochemistry analyses about gene silencing and apoptosis induction were detected.

ResultsElectrophoresis experiment revealed that PEI could condense DNA efficiently. The application of UTMD significantly increases the tissue transfection. Both expression vectors showed that gene expressions were present in all sections of tumors that received ultrasound exposure but not in control tumors. More importantly, the increases in transgene expression were related to UTMD with the presence of PEI significantly. Silencing of the survivin gene could induce apoptosis effectively by downregulating survivin and bcl-2 expression, also cause up-regulation of bax and caspase-3 expression.

ConclusionsThis noninvasive, novel combination of UTMD with PEI could enhance targeted gene delivery and gene expression in tumor xenografts at intravenous administration effectively without causing any apparently adverse effect, and might be a promising candidate for gene therapy. Silencing of survivin gene expression with shRNA could be facilitated by this non-viral technique, and lead to significant cell apoptosis.

Electronic supplementary materialThe online version of this article doi:10.1186-1756-9966-29-152 contains supplementary material, which is available to authorized users.

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Autor: Zhi-Yi Chen - Kun Liang - Ri-Xiang Qiu

Fuente: https://link.springer.com/







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