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.
Highlights
Cucurbit[n]urils (CB[n]s) are barrel-shaped macrocycles that may form host–guest complexes with drugs and, may be used as nanosized vehicles for drug delivery.To date, CB[n]s have been reported to form complexes with a variety of pharmaceuticals, including prilocain [1], isoniazid [2], sanguinarine [3], berberine [4], pilocarpine [5], tuftsin [6], mitoxantrone [7], methotrexate [8] and other peptides or proteins [9]
Based on the effect of carboplatin with CB[7] on Peripheral blood mononuclear cells (PBMCs) and K562, we suggested that that adding CB[7] did not enhance the cytotoxic effect of carboplatin on cells that derived adding CB[7] did not enhance the cytotoxic effect of carboplatin on cells that derived from from hematopoietic stem cells
Carboplatin was purchased from Tokyo Chemical Industry Co., (Tokyo, Japan), and oxaliplatin was purchased from Biomol (Hamburg, Germany)
Summary
Cucurbit[n]urils (CB[n]s) are barrel-shaped macrocycles that may form host–guest complexes with drugs and, may be used as nanosized vehicles for drug delivery.To date, CB[n]s have been reported to form complexes with a variety of pharmaceuticals, including prilocain [1], isoniazid [2], sanguinarine [3], berberine [4], pilocarpine [5], tuftsin [6], mitoxantrone [7], methotrexate [8] and other peptides or proteins [9]. The effect of complexation with CB[n] on the biological properties of encapsulated drugs was studied and discussed [10]. With anticancer drugs based on metal complexes, primarily platinum (II). CB[7] forms complexes with various platinum compounds, and complexation can enhance the antitumor effect of the drug and reduce side effects [11].The most studied system of this type is the complex of CB[7] (Figure 1) with cisplatin [12]. In vivo studies have shown that the complexation with CB[n] reduces the toxic side effects of cisplatin [13,14]. Complexation with CB[7] does not lead to a decrease in the cytotoxic activity of cisplatin
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