A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours

作者：Mercado Lubo Regino; Zhang Yuanwei; Zhao Liang; Rossi Kyle; Wu Xiang; Zou Yekui; Castillo Antonio; Leonard Jack; Bortell Rita; Greiner Dale L; Shultz Leonard D; Han Gang^*; McCormick Beth A^*

来源：Nature Communications, 2016, 7(1): 12225.

DOI：10.1038/ncomms12225

Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

• 出版日期2016-7