Pemetrexed-conjugated hyaluronan for the treatment of malignant pleural mesothelioma

被引:9
作者
Amano, Yuki [1 ]
Ohta, Seiichi [2 ]
Sakura, Kazuma L. [3 ,4 ]
Ito, Taichi [1 ,2 ]
机构
[1] Univ Tokyo, Dept Chem Syst Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan
[2] Univ Tokyo, Ctr Dis Biol & Integrat Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan
[3] Osaka Univ Hosp, Resp Ctr, Suita, Osaka 5650871, Japan
[4] Osaka Univ, Dept Surg, Suita, Osaka 5650871, Japan
关键词
Anti-tumor; Drug conjugates; Pemetrexed; Malignant pleural mesothelioma; DIHYDROFOLATE REDUCTASES; PERITONEAL DISSEMINATION; MOLECULAR-WEIGHT; FOLIC-ACID; FOLATE; DOXORUBICIN; INHIBITION; CISPLATIN; CYTOTOXICITY; THYMIDYLATE;
D O I
10.1016/j.ejps.2019.105008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Pemetrexed (PMX) is a multi-targeted antifolate drug used for the treatment of malignant pleural mesothelioma (MPM) and non-small cell lung cancer. Hyaluronan (HA) in blood is well known as a disease marker of MPM. We synthesized PMX-conjugated hyaluronan (HA-ADH-PMX) for the first time to develop a novel anticancer chemotherapeutic agent. HAs with different molecular weights (76 and 130 kDa) were first derivatized with adipic dihydrazide (ADH) and then conjugated to PMX. The obtained HA-ADH-PMX retained inhibitory activity against folate metabolism enzymes; thymidylate synthase was inhibited to the same extent as native PMX, whereas the inhibition constant against dihydrofolate reductase was 3.3% for 76 kDa HA-ADH-PMX and 12% for 130 kDa HA-ADH-PMX when compared with that of native PMX. The in vitro cytotoxicity of HA-ADH-PMX from both molecular weights against MPM cell lines was lower than that of native PMX. On the other hand, intrapleural administration of 76 kDa HA-ADH-PMX resulted in a survival rate of MPM model mice comparable to that with native PMX, suggesting the potential for future MPM therapy.
引用
收藏
页数:10
相关论文
共 48 条
[21]   Novel hyaluronic acid-methotrexate conjugates for osteoarthritis treatment [J].
Homma, Akie ;
Sato, Haruhiko ;
Okamachi, Akira ;
Emura, Takashi ;
Ishizawa, Takenori ;
Kato, Tatsuya ;
Matsuura, Tetsu ;
Sato, Shigeo ;
Tamura, Tatsuya ;
Higuchi, Yoshinobu ;
Watanabe, Tomoyuki ;
Kitamura, Hidetomo ;
Asanuma, Kentaro ;
Yamazaki, Tadao ;
Ikemi, Masahisa ;
Kitagawa, Hironoshin ;
Morikawa, Tadashi ;
Ikeya, Hitoshi ;
Maeda, Kazuaki ;
Takahashi, Koichi ;
Nohmi, Kenji ;
Izutani, Noriyuki ;
Kanda, Makoto ;
Suzuki, Ryochi .
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (13) :4647-4656
[22]   Characterization and comparative studies of zebrafish and human recombinant dihydrofolate reductases - Inhibition by folic acid and polyphenols [J].
Kao, Tseng-Ting ;
Wang, Kuan-Chieh ;
Chang, Wen-Ni ;
Lin, Chia-Ying ;
Chen, Bing-Hung ;
Wu, Hua-Lin ;
Shi, Guey-Yueh ;
Tsai, Jen-Ning ;
Fu, Tzu-Fun .
DRUG METABOLISM AND DISPOSITION, 2008, 36 (03) :508-516
[23]   Hyaluronic acid-paclitaxel conjugate micelles: Synthesis, characterization, and antitumor activity [J].
Lee, Hyukjin ;
Lee, Kyuri ;
Park, Tae Gwan .
BIOCONJUGATE CHEMISTRY, 2008, 19 (06) :1319-1325
[24]   Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for cancer cell targeting [J].
Li, Ming-Hsin ;
Choi, Seok Ki ;
Thomas, Thommey P. ;
Desai, Ankur ;
Lee, Kyung-Hoon ;
Kotlyar, Alina ;
Holl, Mark M. Banaszak ;
Baker, James R., Jr. .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 47 :560-572
[25]   Hyaluronan production increases the malignant properties of mesothelioma cells [J].
Li, Y ;
Heldin, P .
BRITISH JOURNAL OF CANCER, 2001, 85 (04) :600-607
[26]   Antitumor and antimetastatic effects of pemetrexed-loaded targeted nanoparticles in B16 bearing mice [J].
Lu, Nannan ;
Li, Rutian ;
Liu, Qin ;
Hu, Bing ;
Xu, Xiaoling ;
Ji, Chushu ;
Han, Xinghua ;
Wang, Pin ;
Liu, Baorui .
DRUG DELIVERY, 2016, 23 (07) :2566-2574
[27]   Targeted delivery of doxorubicin by HPMA copolymer-hyaluronan bioconjugates [J].
Luo, Y ;
Bernshaw, NJ ;
Lu, ZR ;
Kopecek, J ;
Prestwich, GD .
PHARMACEUTICAL RESEARCH, 2002, 19 (04) :396-402
[28]   Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate [J].
Luo, Y ;
Prestwich, GD .
BIOCONJUGATE CHEMISTRY, 1999, 10 (05) :755-763
[29]   Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer [J].
Misra, Suniti ;
Hascall, Vincent C. ;
Markwald, Roger R. ;
Ghatak, Shibnath .
FRONTIERS IN IMMUNOLOGY, 2015, 6
[30]   Kinetics of the inhibition of bovine liver dihydrofolate reductase by tea catechins:: Origin of slow-binding inhibition and pH studies [J].
Navarro-Perán, E ;
Cabezas-Herrera, J ;
Hiner, ANP ;
Sadunishvili, T ;
García-Cánovas, F ;
Rodríguez-López, JN .
BIOCHEMISTRY, 2005, 44 (20) :7512-7525