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. 2014 Oct;103(10):3235-43.
doi: 10.1002/jps.24083. Epub 2014 Jul 16.

Enhanced bacterial tumor delivery by modulating the EPR effect and therapeutic potential of Lactobacillus casei

Jun Fang  1 , Long Liao, Hongzhuan Yin, Hideaki Nakamura, Takashi Shin, Hiroshi Maeda
Affiliations

Enhanced bacterial tumor delivery by modulating the EPR effect and therapeutic potential of Lactobacillus casei

Jun Fang et al. J Pharm Sci. 2014 Oct.

Abstract

Bacteria of micrometer size could accumulate in tumor based on enhanced permeability and retention (EPR) effect. We report here Lactobacillus casei (L. casei), a nonpathogenic facultatively anaerobic bacterium, preferentially accumulated in tumor tissues after intravenously (i.v.) injection; at 24 h, live bacteria were found more in the tumor, whereas the bacteria in normal tissues including the liver and spleen were cleared rapidly. The tumor-selective accumulation and growth of L. casei is probably due to the EPR effect and the hypoxic tumor environment. Moreover, the bacterial tumor delivery was significantly increased by a nitric oxide (NO) donor nitroglycerin (NG, 10-70 times) and an angiotensin II converting enzyme inhibitor, enalapril (6-18 times). Consequently significant suppression of tumor growth was found in a colon cancer C26 model, and more remarkable antitumor effect was achieved when L. casei was combined with NG, probably by modulating the host nonspecific immune responses; tumor necrosis factor-α significantly increased in tumor after the treatment, as well as NO synthase activity and myleoperoxidase activity. These findings suggest the potential of L. casei as a candidate for targeted bacterial antitumor therapy, especially in combine with NG or other vascular mediators.

Keywords: ACE inhibitor; Cancer; Distribution; EPR effect; Lactobacillus casei; Nanotechnology; Permeability; Targeted drug delivery; nitroglycerin; vascular permeability.

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