Cisplatin-Chelated Iminodiacetic Acid-Conjugated Hyaluronic Acid Nanogels for the Treatment of Malignant Pleural Mesothelioma in Mice

被引：10

作者：

Amano, Yuki ^{[1
]}

Sakura, Kazuma L. ^{[2
,3
]}

Ohta, Seiichi ^{[1
,4
,5
]}

Ito, Taichi ^{[1
,4
]}

机构：

[1] Univ Tokyo, Dept Chem Syst Engn, Tokyo 1138656, Japan

[2] Osaka Univ Hosp, Resp Ctr, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Dept Surg, Suita, Osaka 5650871, Japan

[4] Univ Tokyo, Ctr Dis Biol & Integrat Med, Tokyo 1130033, Japan

[5] Univ Tokyo, Inst Engn Innovat, Tokyo 1138656, Japan

来源：

MOLECULAR PHARMACEUTICS | 2022年 / 19卷 / 03期

关键词：

hyaluronic acid; cisplatin; nanogel; injectable hydrogel; malignant pleural mesothelioma; EXPRESSION; NANOPARTICLES; INCREASES; SYNTHASES; SIZE;

D O I：

10.1021/acs.molpharmaceut.1c00797

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Malignant pleural mesothelioma (MPM) is one of the intractable cancers that require a more effective therapeutic strategy for clinical practice. Hyaluronic acid (HA) nanogels were prepared by the chelation of cisplatin (CDDP) with different molecular weights of iminodiacetic acid-conjugated hyaluronic acid (HA-IDA). The sizes of the 100, 850, and 2000 kDa HA nanogels were 33, 43, and 44 nm, respectively. MSTO-211H, a human MPM cell line, was more effective in taking up all three HA nanogels compared to AB22, a mouse MPM cell line. In addition, the 850 kDa HA nanogel showed higher anticancer activity against AB22 and MSTO-211H than 100 and 2000 kDa HA nanogels. Furthermore, all the HA nanogels showed a milder cytotoxic effect on normal Met-5A mesothelial cells compared to that exhibited by free CDDP. Finally, the 850 kDa HA nanogel was administrated intrapleurally into both the MSTO-211H xenograft and AB22 allograft mouse models of MPM using an injectable HA-based hydrogel. HA nanogels showed a significant therapeutic effect in both the xenograft and allograft models.

引用

页码：853 / 861

页数：9

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