Vernazza Stefania, Dellacasa Elena, Tirendi Sara, Pastorino Laura, Bassi Anna Maria
Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genoa, 16145 Genoa, Italy.
Nanomaterials (Basel). 2021 May 21;11(6):1365. doi: 10.3390/nano11061365.
Cisplatin is a first-choice chemotherapeutic agent used to treat solid tumors even though the onset of multi-drug resistance and the time-dose side-effects impair its mono-therapeutic application. Therefore, new drug-delivery approaches, based on nanomedicine strategies, are needed to enhance its therapeutic potential in favor of a dose-reduction of cisplatin. Polyunsaturated fatty acids and their metabolism-derived intermediates, as well as lipid peroxidation end-products, are used as adjuvants to improve the effectiveness of chemotherapy. Lipid hydroperoxides, derived from the oxidation of edible oils, can contribute to cell death, generating breakdown products (e.g., reactive aldehydes). In this regard, the aim of this present study was to evaluate an invitro combinatory strategy between a lecithin-based nanoemulsion system of K600, a patented mixture of peroxidated oil and peroxidated cholesterol, and cisplatin on DLD1 human adenocarcinoma cells. Our findings showed that nanoemulsions, acting in synergy with cisplatin, improve cisplatin bioactivity, in terms of enhancing its anti-cancer activity, towards DLD1 cells. Indeed, this combination approach, whilst maintaining cisplatin at low concentrations, induces a significant reduction in DLD1 cell viability, an increase in pro-apoptotic markers, and genotoxic damage. Therefore, K600 nanoemulsions as an efficient targeted delivery system of cisplatin allow for the reduction in the chemotherapeutic agent doses.
顺铂是治疗实体瘤的一线化疗药物，尽管多药耐药的出现以及时间-剂量副作用限制了其单药治疗的应用。因此，需要基于纳米医学策略的新型药物递送方法来提高其治疗潜力，以降低顺铂的剂量。多不饱和脂肪酸及其代谢衍生中间体以及脂质过氧化终产物被用作佐剂以提高化疗效果。食用油氧化产生的脂质氢过氧化物可导致细胞死亡，产生分解产物（如活性醛）。在这方面，本研究的目的是评估基于卵磷脂的纳米乳液系统K600（一种专利的过氧化油和过氧化胆固醇混合物）与顺铂对DLD1人腺癌细胞的体外联合策略。我们的研究结果表明，纳米乳液与顺铂协同作用，在增强其对DLD1细胞的抗癌活性方面提高了顺铂的生物活性。实际上，这种联合方法在将顺铂维持在低浓度的同时，可显著降低DLD1细胞活力，增加促凋亡标志物，并造成基因毒性损伤。因此，K600纳米乳液作为顺铂的有效靶向递送系统可降低化疗药物剂量。
