Abstract
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.
Highlights
The success of chemotherapy is restricted by multi-drug resistance (MDR) within cancer cells
6 mg/mL
Radiotherapy, today still show limited efficacy due to their side effects [50]. Whenwhen such such traditional approaches are used as a single modality, they they do not traditional approaches are used as a single modality, donecessarily not necessarily provide satisfactory outcomes, as in the case of surgery, where it is not always possiblepossible to provide satisfactory outcomes, as in the case of surgery, where it is not always to carry out a complete tumor lesion resection [51], or in the case of chemotherapy and radiotherapy, where there is the onset of both MDR [52,53] and the insensitivity of hypoxic cancer cells to ionizing radiation [54,55]
Summary
The success of chemotherapy is restricted by multi-drug resistance (MDR) within cancer cells. Cisplatin is still a first-choice chemotherapy for several cancer treatments despite the onset of MDR and time–dose side-effects impairing its monotherapeutic application [1,2,3,4,5] In this regard, several previous studies have shown that, to reach a better therapeutic efficacy, it is necessary to exploit the synergy between drugs and to develop new drugdelivery approaches based on nanomedicine [6,7]. Several previous studies have shown that, to reach a better therapeutic efficacy, it is necessary to exploit the synergy between drugs and to develop new drugdelivery approaches based on nanomedicine [6,7] It is well-known that most chemotherapeutic agents through redox regulation enhance the intracellular oxidative stress rate, leading to cancer cell death (i.e., arsenic trioxide, doxorubicin, and PEITC) [8,9,10,11]
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