信息来源：
http://www.natureasia.com/zh-cn/nature/highlights/86742
http://www.nature.com/nature/journal/v546/n7659/full/nature22341.html
KRas突变体是一种常见的胰腺癌驱动因素，利用siRNA减少其表达是一种预防胰腺肿瘤生长的可能方法。Raghu Kalluri及同事借助外泌体提升了siRNA向胰腺的递送，并表明这些内源性囊泡可以比人工脂质体更好地避开免疫清除，原因可能是其膜内的CD47表达。胰腺肿瘤细胞倾向于摄取经过改造的外泌体（iExosome）。作者认为，这种摄取受到了巨胞饮作用增强的推动。在胰腺癌小鼠模型中，iExosome能够降低KRas致瘤信号转导，减少肿瘤生长。
Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer
Sushrut Kamerkar,Valerie S. LeBleu,Hikaru Sugimoto,Sujuan Yang, Carolina F. Ruivo, Sonia A. Melo,J. Jack Lee & Raghu Kalluri
Nature 546, 498–503 (22 June 2017) doi:10.1038/nature22341
The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic KrasG12D, a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.
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