title: Nanoparticulation of BCG-CWS for application to bladder cancer therapy.
abstract: The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukiage
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Japan BCG Central Laboratory, Kiyose, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakaya
authors.affiliation: Japan BCG Central Laboratory, Kiyose, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Yano
authors.affiliation: Department of Urology, Faculty of Medicine, Tsukuba University, Tsukuba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Faculty of Medicine, Tsukuba University, Tsukuba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.affiliation: Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002085:Butylhydroxybutylnitrosamine; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D017358:Cell Wall Skeleton / Q000008:administration & dosage*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D017358:Cell Wall Skeleton; D002085:Butylhydroxybutylnitrosamine
keywords: BCG-CWS; Bladder cancer; Cancer immunotherapy; Delivery system; Nanoparticle; Packaging