Login to Access Video or Poster Abstract: MP88-16
Sources of Funding: China Postdoctoral Science Foundation (2016M591831)

Introduction

Bladder cancer is the most common malignancy of urogenital system and one of the major causes of death in Chinese cancer patients. Small RNAs (sRNA) are potential therapeutic drugs for bladder cancers. However, it is still difficult to transport sRNAs stably in the body. Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools._x000D_

Methods

In the present study, we employed modified exosomes expressing the iRGD peptide (a tumor-penetrating peptide) on the membrane surface to deliver Survivin siRNA into bladder cancer in a mouse xenograft tumor model. qPCR and western blotting were used to determine the expression of siRNA and survivin in tumor tissues._x000D_

Results

We found that Survivin siRNA could be efficiently packaged into iRGD modified exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered Survivin siRNA into 5637 bladder cancer cells and the mouse xenograft tumor. Functionally, Survivin siRNA-loaded iRGD exosomes significantly reduced Survivin mRNA and protein levels in bladder cancer cells. Sebsequently, Survivin siRNA delivered by the iRGD modified exosomes strongly inhibited the growth of the mouse xenograft tumor._x000D_

Conclusions

In conclusion, our results demonstrate that targeted iRGD exosomes can efficiently transfer siRNA to bladder cancer and mediate the growth inhibiton of bladder cancer by downregulating Survivin expression levels. Our study provides a brand new strategy to treat bladder cancer._x000D_

Funding

China Postdoctoral Science Foundation (2016M591831)