Enhanced Bacterial Tumor Delivery by Modulating the EPR Effect and Therapeutic Potential of Lactobacillus casei. Issue 10 (16th July 2014)

• Record Type: Journal Article
• Authors: Fang, Jun; Liao, Long; Yin, Hongzhuan; Nakamura, Hideaki; Shin, Takashi; Maeda, Hiroshi
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 10(2014:Oct.)
• Page Start: 3235
• Page End: 3243
• Publication Date: 2014-07-16
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24083
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Bacteria of micrometer size could accumulate in tumor based on enhanced permeability and retention (EPR) effect. We report here <italic>L</italic><italic>actobacillus casei</italic> (<italic>L. casei</italic>), 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 <italic>L. casei</italic> 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 <italic>L</italic>. <italic>casei</italic> 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 <italic>L</italic>. <italic>casei</italic> as a candidate for targeted bacterial antitumor therapy, especially in combine with NG or other vascular mediators. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3235–3243, 2014</p> </abstract>