Vítejte v CucurbitAgent

The clinical application of camptothecin (CPT) is limited by poor solubility and severe toxicity. This study compares the therapeutic performance of a cucurbit[7]uril-based CPT complex (CB[7]-CPT) with free CPT and β-cyclodextrin-CPT (β-CD-CPT) in colorectal cancer models. In vitro, free CPT, β-CD-CPT, and CB[7]-CPT were tested on normal LO2 and cancerous HCT116 cells. CB[7] encapsulation reduced toxicity toward normal LO2 cells (IC50: 0.47 μM, ∼25-fold higher than the IC50 of free CPT) while improving potency against HCT116 cells (CB[7]-CPT IC50: 0.24 μM; free CPT IC50: 0.55 μM, ∼2-fold more potent than free CPT). The selectivity index improved from 0.034 (CPT) to 1.976 (CB[7]-CPT), indicating a wide safety margin. Apoptosis assays confirmed that CB[7]-CPT induced significantly greater apoptotic cell death at equivalent concentrations than either free CPT or β-CD-CPT. In HCT116 xenograft models, CB[7]-CPT achieved a tumor inhibition rate of 76%, markedly outperforming free CPT (46%) and β-CD-CPT (62%). This enhanced efficacy was accompanied by increased intratumoral apoptosis, reduced proliferation, and decreased microvessel density. Importantly, CB[7]-CPT markedly attenuated liver, kidney, and gastrointestinal toxicity typically associated with CPT exposure. Pharmacokinetically, CB[7]-CPT displayed a 1.94-fold higher AUC and a 1.59-fold prolonged elimination half-life relative to free CPT, reflecting extended circulation and improved systemic exposure. These findings collectively establish CB[7]-CPT as a highly effective and safer alternative not only to free CPT but also to conventional cyclodextrin-based formulations, demonstrating enhanced selectivity, robust pro-apoptotic activity, and a superior safety profile.

The melon fly, Zeugodacus cucurbitae (Coquillett), is a major pest of cucurbitaceous fruits, and insecticides are widely used for its management. However, sometimes environmental factors may reduce insecticide deposits below lethal levels, and adult flies may receive only partial exposure during spraying, resulting in exposure to non-lethal doses. This study evaluated the reproductive fitness of Z. cucurbitae survivors following LD20 exposure to commercially available formulations of fipronil, spinosad, and malathion. Adult flies surviving topical LD20 treatment were assigned to 4 treatment combinations: (1) treated female and treated male (F+M+), (2) treated female and untreated male (F+M-), (3) untreated female and treated male (F-M+), and (4) untreated female and untreated male (F-M-). Malathion (0.18 μg/fly) exerted the most pronounced effects on Z. cucurbitae, significantly reducing mating frequency, progeny production, and adult longevity of treated flies, while increasing the proportion of malformed offspring. In contrast, fipronil (0.04 μg/fly) and spinosad (0.005 μg/fly) exhibited significant effects only when both sexes were treated. Notably, LD20 treatment with malathion enhanced the mating competitiveness of treated female flies, indicating a potential stimulatory effect. The findings suggest that LD20 of malathion had a significant impact on the reproductive fitness of melon flies, even when only 1 of the sexes was treated. In contrast, spinosad and fipronil produced adverse effects only when both sexes were treated, with minimal effects observed when only 1 sex was treated.