The Effect of Cucurbit[7]uril on the Antitumor and Immunomodulating Properties of Oxaliplatin and Carboplatin

Int J Mol Sci. 2021 Jul 8;22(14):7337. doi: 10.3390/ijms22147337.

Abstract

Cucurbit[7]uril (CB[7]) is a molecular container that may form host-guest complexes with platinum(II) anticancer drugs and modulate their efficacy and safety. In this paper, we report our studies of the effect of CB[7]-oxaliplatin complex and the mixture of CB[7] and carboplatin (1:1) on viability and proliferation of a primary cell culture (peripheral blood mononuclear cells), two tumor cell lines (B16 and K562) and their activity in the animal model of melanoma. At the same time, we studied the impact of platinum (II) drugs with CB[7] on T cells and B cells in vitro. Although the stable CB[7]-carboplatin complex was not formed, the presence of cucurbit[7]uril affected the biological properties of carboplatin. In vivo, CB[7] increased the antitumor effect of carboplatin, but, at the same time, increased its acute toxicity. Compared to free oxaliplatin, its complex with CB[7] shows a greater cytotoxic effect on tumor cell lines B16 and K562, while in vivo, the effects of the free drug and encapsulated drug were comparable. However, in vivo studies also demonstrated that the encapsulation of oxaliplatin in CB[7] lowered the toxicity of the drug.

Keywords: carboplatin; cell viability; cucurbit[7]uril; oxaliplatin; supramolecular complex.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Carboplatin / pharmacology*
  • Female
  • Humans
  • Imidazoles / pharmacology*
  • Immunologic Factors / pharmacology*
  • K562 Cells
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Mice
  • Organoplatinum Compounds / pharmacology*
  • Pyridines / pharmacology*

Substances

  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • Imidazoles
  • Immunologic Factors
  • Organoplatinum Compounds
  • Pyridines
  • cucurbit(7)uril
  • oxiplatin
  • Carboplatin