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

Mol Pharm. 2022 Mar 7;19(3):853-861. doi: 10.1021/acs.molpharmaceut.1c00797. Epub 2022 Feb 10.


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.

Keywords: cisplatin; hyaluronic acid; injectable hydrogel; malignant pleural mesothelioma; nanogel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cisplatin* / pharmacology
  • Cisplatin* / therapeutic use
  • Humans
  • Hyaluronic Acid
  • Imino Acids
  • Mesothelioma, Malignant*
  • Mice
  • Nanogels


  • Imino Acids
  • Nanogels
  • Hyaluronic Acid
  • Cisplatin
  • iminodiacetic acid