Abstract

The radiation sensitivity of tumor cells is closely related to tumor cell hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is considered a key transcription factor which regulates the sensitivity of hypoxic tumor cells to radiotherapy. On the other hand, some studies have shown that gold nanomaterials improve radiation sensitivity. However, studies on the effect of gold nanomaterials carrying HIF-1αsiRNA on tumor radiotherapy, and the underlying mechanisms are limited. Thus, the present study was aimed at investigating the effect of gold nanocomposites (AuNRs) carrying HIF-1αsiRNA (AuNRs-HIF-1αsiRNA) on the radiation sensitivity of nasopharyngeal carcinoma (NPC) hypoxia cells. The effect of AuNRs-HIF-1αsiRNA on radiation sensitivity of hypoxic NPC cells was determined under X-ray irradiation. The results showed that Au-HIF-1αsiRNA improved the radio-sensitivity of NPC tumor. Thus, this study has demonstrated that gold nanomaterials carrying HIF-1αsiRNA effectively increased the radio-sensitivity of hypoxic tumor, thereby improving the effect of radiotherapy on NPC cells.

Highlights

  • The incidence of nasopharyngeal carcinoma (NPC) in Asian countries is generally high, and most NPC patients are subjected to irradiation therapy

  • These results indicate that the gold nanorod complex (AuNRs/ AuNRs-HIF-1αsiRNA) did not exhibit significant toxic accumulation in organs such as the liver and kidney

  • Au-HIF-1αsiRNA group was incorporated into this study, and it was demonstrated it was more effective in enhancing the radiosensitivity of hypoxic NPC cells

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Summary

Introduction

The incidence of nasopharyngeal carcinoma (NPC) in Asian countries is generally high, and most NPC patients are subjected to irradiation therapy. Previous studies have shown that HIF-1 is a key transcription factor involved in tumor hypoxia adaptation [3]. It is composed of HIF-1α subunit and HIF-1β subunit, but its function is determined mainly by the stability and activity of the HIF-1α subunit. HIF-1α is overexpressed, which induces the expression of related downstream genes, thereby enhancing the adaptation of tumor cells to hypoxia, and increasing their resistance to damaging effects of radiotherapy [4, 5]. The technique of RNA interference (RNAi), an emerging gene knockout technology with high specificity and efficiency, has been widely used in many fields It is a small interfering RNA (siRNA) which promotes silencing of targeted HIF-1α mRNA, thereby down-regulating the expression of the target gene [6]. The present research was focused on how to safely and effectively carry out targeted delivery of siRNA molecules into the cell

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