title: Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect.
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.
authors: Research Institute for Drug Delivery System, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan.
authors: Jun
authors: J
authors: Fang
authors: Research Institute for Drug Delivery System, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan.
authors: Liao
authors: L
authors: Long
authors: Research Institute for Drug Delivery System, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan. hirmaeda@ph.sojo-u.ac.jp.|Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi Ward, Kumamoto, Kumamoto Prefecture, 860-0082, Japan. hirmaeda@ph.sojo-u.ac.jp.
authors: Hiroshi
authors: H
authors: Maeda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001419:Bacteria / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D046911:Macromolecular Substances / Q000008:administration & dosage / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005996:Nitroglycerin / Q000378:metabolism*; D010539:Permeability; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D046911:Macromolecular Substances; D005996:Nitroglycerin
keywords: EPR effect; Lactobacillus casei; Macromolecules; Nitric oxide; Nitroglycerin; Solid tumors