Title

A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

Document Type

Article

Publication Date

7-25-2016

JAX Source

Nat Commun 2016 Jul 25; 7:12225

Volume

7

First Page

12225

Last Page

12225

ISSN

2041-1723

PMID

27452236

Grant

1R24OD018259, CA034196

Abstract

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. Nat Commun 2016 Jul 25; 7:12225.

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