A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours

Mercado–Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle C.; Wu, Xiang; Zou, Yekui; Castillo, Antonio del; Leonard, Jack L.; Bortell, Rita; Greiner, Dale L.; Shultz, Leonard D.; Han, Gang; McCormick, Beth A.

doi:10.1038/ncomms12225

Cited by 68 publications

(43 citation statements)

References 50 publications

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“…(G-I) Total lamina propria leukocytes were isolated and stained for flow cytometry. Neutrophils were characterized as live/ CD45 + CD11b hi In parallel with increased MRP2 levels, another luminal ABC transporter restricted to the luminal epithelial surface, P-glycoprotein (P-gp), is actively reduced at the epithelial surface by Salmonella typhimurium (16,17), the significance of which was previously unclear. P-gp is a multidrug transporter known to efflux small neutral or positively charged hydrophobic compounds (18).…”

Section: Resultsmentioning

confidence: 99%

Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis

Szabady

Louissaint

Lubben

et al. 2018

Journal of Clinical Investigation

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Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted multidrug resistance transporter P-glycoprotein (P-gp) and reveal a mechanism, which we believe is novel, for endocannabinoid secretion into the intestinal lumen. Knockdown or inhibition of P-gp reduced luminal secretion levels of N-acyl ethanolamine-type endocannabinoids, which correlated with increased neutrophil transmigration in vitro and in vivo. Additionally, loss of CB2, the peripheral cannabinoid receptor, led to increased pathology and neutrophil influx in models of acute intestinal inflammation. These results define a key role for epithelial cells in balancing the constitutive secretion of antiinflammatory lipids with the stimulated secretion of proinflammatory lipids via surface efflux pumps in order to control neutrophil infiltration into the intestinal lumen and maintain homeostasis in the healthy intestine.

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Section: Resultsmentioning

confidence: 99%

Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis

Szabady

Louissaint

Lubben

et al. 2018

Journal of Clinical Investigation

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“…For instance, NPs mimicking Salmonella have been engineered by McCormick et al . 48 . The Salmonella mimics were constructed from gold NPs coated with the S. typhimurium type III secreted effector protein SipA, which reduces the function of P-gp.…”

Section: Circumvention Of Tumor Drug Resistancementioning

confidence: 99%

Nanoparticle-based drug delivery systems: What can they really do in vivo?

et al. 2017

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In the past few decades, there has been explosive growth in the construction of nanoparticle-based drug delivery systems (NDDSs), namely nanomedicines, owing to their unique properties compared with traditional drug formulations. However, because of a variety of challenges, few nanomedicines are on sale in the market or undergoing clinical trial at present. Thus, it is essential to look back and re-evaluate what these NDDSs can really do in vivo, why nanomedicines are regarded as potential candidates for next-generation drugs, and what the future of nanomedicine is. Here, we focus mainly on the properties of NDDSs that extend blood circulation, enhance penetration into deep tumor tissue, enable controllable release of the payload into the cytoplasm, and overcome multi-drug resistance. We further discuss how to promote the translation of nanomedicines into reality. This review may help to identify the functions of NDDSs that are really necessary before they are designed and to reduce the gap between basic research and clinical application.

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“…By mimicking the ability of Salmonella enterica serotype Typhimurium pathogen to reverse multidrug resistance, a semi-synthetic 'Salmonella nanoparticle mimic' based on gold nanoparticle packaged with effector protein (SipA) has been constructed by Mercado-Lubo R. et al (2016). The system could suppressed the growth of tumour by reducing the P-glycoprotein, a multidrug resistance transporter, at a SipA dose significantly lower than the free SipA and increases tumour sensitivity to conventional chemotherapeutics.…”

Section: Medical and Pharmaceuticalmentioning

confidence: 99%

Nanoparticles Carrying Biological Molecules: Recent Advances and Applications

Saallah

Lenggoro

2018

KONA

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In the past few decades, enormous advances have been achieved in the field of particle technology and the trend has been shifted from macro to micro and recently to the nanoscale. Integration of nanotechnology and biotechnology has paved the way to the development of biological nanoparticles, derived from biomolecules, and biomolecule-nanoparticle conjugates for numerous applications. This review provides an overview of various types of biological nanoparticles and the methods of their fabrication with primary emphasis on the drying methods, particularly on the newly emerging technique, the electrospraying. Recent advances in the integration of biomolecules with nanoparticles in the past five years to present are also discussed. Finally, the application of the biomolecule-nanoparticle conjugates in various fields including medicals and pharmaceuticals, biosensors and bioelectronics, foods, and agricultures are also highlighted.

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A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours

Cited by 68 publications

References 50 publications

Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis

Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis

Nanoparticle-based drug delivery systems: What can they really do in vivo?

Nanoparticles Carrying Biological Molecules: Recent Advances and Applications

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