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Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect

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Bacterial Therapy of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1409))

Abstract

The use of bacteria, about 1 μm in size, is now becoming an attractive strategy for cancer treatment. Solid tumors exhibit the enhanced permeability and retention (EPR) effect for biocompatible macromolecules such as polymer-conjugated anticancer agents, liposomes, and micelles. This phenomenon permits tumor-selective delivery of such macromolecules. We report here that bacteria injected intravenously evidenced a property similar to that can of these macromolecules. Bacteria that can accumulate selectively in tumors may therefore be used in cancer treatment.

Facultative or anaerobic bacteria will grow even under the hypoxic conditions present in solid tumors. We found earlier that nitric oxide (NO) was among the most important factors that facilitated the EPR effect via vasodilatation, opening of endothelial cell junction gaps, and increasing the blood flow of hypovascular tumors. Here, we describe the augmentation of the EPR effect by means of nitroglycerin (NG), a commonly used NO donor, using various macromolecular agents in different tumor models. More importantly, we report that NG significantly enhanced the delivery of Lactobacillus casei to tumors after intravenous injection of the bacteria, more than a tenfold increase in bacterial accumulation in tumors after NG treatment. This finding suggests that NG has a potential advantage to enhance bacterial therapy of cancer, and further investigations of this possibility are warranted.

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Acknowledgment

This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Culture, Sports and Technology of Japan (No. 08011717), a Cancer Speciality grant from the Ministry of Health, Welfare and Labour (H23-Third Term Comprehensive Control Research, General-001), and research funds of the Faculty of Pharmaceutical Sciences at Sojo University.

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Authors and Affiliations

  1. Research Institute for Drug Delivery System, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan

    Jun Fang, Liao Long & Hiroshi Maeda

  2. Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan

    Hiroshi Maeda

Authors
  1. Jun Fang
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  2. Liao Long
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  3. Hiroshi Maeda
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Correspondence to Hiroshi Maeda .

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Editors and Affiliations

  1. Department of Surgery, AntiCancer Inc, Univ of California – San Diego, San Diego, California, USA

    Robert M Hoffman

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Fang, J., Long, L., Maeda, H. (2016). Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect. In: Hoffman, R. (eds) Bacterial Therapy of Cancer. Methods in Molecular Biology, vol 1409. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3515-4_2

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  • DOI: https://doi.org/10.1007/978-1-4939-3515-4_2

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3513-0

  • Online ISBN: 978-1-4939-3515-4

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