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Milk exosomes - Natural nanoparticles for siRNA delivery.

Abstract：

:Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5'-32P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable. We demonstrated that the siRNA of loaded exosomes is stable and resist degradation. Our results indicated that siRNAs against target genes ranged from 2 to 10-fold knockdown in expression levels in various cancers. Since mutated KRAS has been implicated in the development of various cancers including lung cancer, we tested a mutant-allele specific siRNA against KRASG12S, in A549 cells. We observed a dose-dependent anti-proliferative activity against A549 cells treated with exosomes carrying siKRASG12S. We observed significant inhibition of A549 tumor xenografts in animals treated with folic acid-functionalized exosomes carrying siKRAS. In summary, milk-derived exosomes represent a viable natural nano-carrier for the delivery of siRNA for therapeutic application against cancer.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Aqil F,Munagala R,Jeyabalan J,Agrawal AK,Kyakulaga AH,Wilcher SA,Gupta RC

doi

10.1016/j.canlet.2019.02.011

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

186-195

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30083-7

journal_volume

449

pub_type

杂志文章

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