title: Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation.
abstract: Nanocarriers have been used for specific delivery of therapeutic agents to solid tumors based on the enhanced permeability and retention in cancerous tissues. Despite metastasis is the main reason of cancer-related death and a priority for nanocarrier-based therapies, the targeting ability of nanocarriers to the metastatic disease is poorly understood, especially for preangiogenic micrometastases as nanocarriers usually use the malignant neovasculature for enhancing their accumulation. Thus, herein, we studied the ability of micellar nanocarriers incorporating (1,2-diaminocyclohexane)platinum(II) (DACHPt) for treating liver metastases of bioluminescent murine colon adenocarcinoma C-26, during overt and preangiogenic metastatic stages. After intravenous injection, DACHPt-loaded micelles (DACHPt/m) effectively inhibited the tumor growth in both metastatic tumor models. While the anticancer activity of the micelles against overt metastases was associated with their selective accumulation in cancerous tissues having neovasculature, the ability of DACHPt/m to target preangiogenic metastases was correlated with the inflammatory microenvironment of the niche. This targeting capability of polymeric micelles to preangiogenic metastasis may provide a novel approach for early diagnosis and treatment of metastases.
authors: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Hailiang
authors: H
authors: Wu
authors: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: horacio@bmw.t.u-tokyo.ac.jp.
authors: Horacio
authors: H
authors: Cabral
authors: Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Kazuko
authors: K
authors: Toh
authors: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors: Peng
authors: P
authors: Mi
authors: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Yi-Chun
authors: YC
authors: Chen
authors: Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Yu
authors: Y
authors: Matsumoto
authors: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Naoki
authors: N
authors: Yamada
authors: Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Xueying
authors: X
authors: Liu
authors: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Hiroaki
authors: H
authors: Kinoh
authors: Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors: Yutaka
authors: Y
authors: Miura
authors: Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors: Mitsunobu R
authors: MR
authors: Kano
authors: Laboratory of Translational Pathology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors: Hiroshi
authors: H
authors: Nishihara
authors: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors: Nobuhiro
authors: N
authors: Nishiyama
authors: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Center for Disease Biology and Integrative Medicine, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors: Kazunori
authors: K
authors: Kataoka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D007249:Inflammation; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008807:Mice, Inbred BALB C; D008823:Micelles; D061206:Neoplasm Micrometastasis / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry
chemical_list: C554217:((1R,2R)-1,2-diaminocyclohexane)platinum(II); D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D011108:Polymers
keywords: Chemotherapy; Cyclooxygenase-2; Drug delivery system; Metastatic niche; Oxaliplatin