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Gold Nanomaterials at Work in Biomedicine *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Xuan Yang, Miaoxin Yang, Pang Bo, Madeline Vara, Younan Xia
Dox is a DNA intercalating agent and topoisomerase II inhibitor, and a commonly used anticancer drug. Li and coworkers fabricated Dox-loaded hollow Au nanospheres (Dox-AuHSs) and tested them for the destruction of MDA-MB-231 melanoma cells [211]. The loading capacity of Dox was estimated to be around 63% (or 1.7 µg of Dox/µg of Au) due to the binding of Dox to both the inner and outer surfaces of AuHSs. Upon irradiation with NIR light, the Dox-AuHSs were able to provide enhanced cell killing performance (with 86.4% of cells being killed) compared to free Dox (77.4%) or the irradiation of drug-free AuHSs (40.6%). The enhancement in cell killing was attributed to a combination of both photothermal ablation and the cytotoxicity of the released Dox molecules. The tumor ablation performance of the Dox-AuHSs was later evaluated by the same group on a mouse tumor model [570, 672]. The experimental results clearly showed that the combined therapy provided more effective, synergistic tumor suppression than any single type of therapy. It is worth pointing out that a lower dose of Dox was required in the combined therapy, which could minimize the toxic side effects of the drug while maintaining the satisfied treatment result.
Monoterpenes-Based Pharmaceuticals: A Review of Applications In Human Health and Drug Delivery Systems
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Plant- and Marine-Based Phytochemicals for Human Health, 2018
Irina Pereira, Aleksandra Zielińska, Francisco J. Veiga, Ana C. Santos, Izabela Nowak, Amélia M. Silva, Eliana B. Souto
Miyashita et al.93 evaluated the combinatory effect between linalool and DOX. DOX is an anthracycline anticarcinogenic agent.101 The molecular mechanism of DOX involves the activation of the ubiquitin-proteasome system that, in turn, regulates the NF-κB transcription factor which promotes cell growth. In some several types of cancer DOX induces an over-activation of NF-κB leading to the promotion of cancer cells survival. They93 investigated the activity of four Humulus lupulus (hop) components (myrcene, α-humulen, β-caryophyllene, and linalool) on DOX permeability in P388 leukemia cells. The combination between linalool (0.01, 0.1, and 1 μM) and DOX (9.0 μM) increased DOX concentration in P388 leukemia cells leading to an increase in DOX cytotoxicity. The oral administration of DOX combined with linalool (DOX—2.0 mg/kg and linalool—1.0 mg/kg) in P388 leukemia tumor-bearing mice significantly decreased the tumor weight in comparison with DOX treated group. Linalool enhanced the anticancer activity of DOX due to its action on Na+dependent nucleoside transporter 3, which increased the transport of DOX leading to an increased in DOX concentration in P388 leukemia cells. The combination of linalool enables the use of lower concentrations of DOX in cancer cells which in turn decreases the adverse effects of this chemotherapeutic agent in normal tissue. Thus, linalool can be applied in cancer chemotherapy as DOX adjuvant in order to improve the quality of life of leukemia cancer patients.
Radio-Electro-Chemotherapy of Cancer: New Perspectives for Cancer Treatment
Published in Pandit B. Vidyasagar, Sagar S. Jagtap, Omprakash Yemul, Radiation in Medicine and Biology, 2017
Pratip Shil, Pandit B. Vidyasagar, Kaushala Prasad Mishra
Initial experiments were performed to study the dose response of DOX on murine fibrosarcoma, grown in the right hind leg of Swiss Mice. Animals were treated with doses of DOX at 0.6, 1.2, and 2.4 mg/kg of body weight. Based on the outcome, a DOX dose of 0.6 mg/kg of body weight was chosen for the combined treatment.
Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy
Published in Drug Delivery, 2022
Muhammad Sohail, Bin Yu, Zheng Sun, Jiali Liu, Yanli Li, Feng Zhao, Daquan Chen, Xin Yang, Hui Xu
The structure characteristics of the two small-molecule drugs may be responsible for such a particular mode of copolymer-drug interaction (Zhang et al., 2018). Chemically DOX is a kind of drug molecule with moderate hydrophilicity. The glycosidic group would contribute to its high water solubility and the preference for attaching to the hydrophilic surface of micelles (Figure 4B). In contrast, the lipophilic DiMC could be entrapped into the inner hydrophobic core of the micelles through strong hydrophobic interaction during amphiphilic self-assembly. Meanwhile, the acidic hydroxyl group in DiMC from keto-enol tautomerism (Sohail et al., 2021a; Jayakumar et al., 2016) could lead to efficient interaction with DOX via its basic amino group (Figure 4C). In view of this, DiMC could be regarded as a vital link that significantly improved the interactions among the copolymer and both drugs, therefore resulting in high encapsulation yields of CPM-DD, particularly a remarkable increase in the encapsulation efficiency of DOX. In fact, DOX alone could barely be encapsulated into micelles under the same conditions since no noticeable Tyndall effect was observed in this system (Figure 3A). The results demonstrated the unique molecular mechanism relating to the construction of CPM-DD, which would significantly contribute to specific characteristics of this complex micellar system, such as the distinct drug release profiles mentioned above (Figure 3F).
Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression
Published in Pharmaceutical Biology, 2022
Yuan Lu, Wen Liu, Ting Lv, Yanli Wang, Ting Liu, Yi Chen, Yang Jin, Jin Huang, Lin Zheng, Yong Huang, Yan He, Yongjun Li
Therefore, in the present study, we have used a mouse model of DOX-induced myocardial injury to investigate the effects and mechanism of ADI. The dosage of DOX was screened in a preliminary experiment using 2, 3 and 4 mg/kg. The 2 mg/kg dose was too low, with no obvious myocardial toxicity observed. About 30% of the mice were intolerant to 4 mg/kg DOX and died during the experiment. Consequently, a dose of 3 mg/kg was selected for the myocardial injury model. The results from scanning electron microscopy after 15 days of repeated DOX administration showed that the cardiomyocytes of the mice were damaged. The mitochondrial morphology in the model group was abnormal, with the mitochondria appearing swollen. The serum levels of CK, CK-MB, AST and LDH in the model group increased significantly, indicating that the cardiomyocytes were seriously damaged. The levels of BNP, a well-recognized marker of heart failure (Kuwahara et al. 2018), in the model mice were significantly increased, suggesting that the mice may have signs of heart failure. We did not, however, use echocardiography to confirm whether heart failure had occurred. Nevertheless, the above points indicate that the DOX-induced myocardial injury model was successfully established and could be used for subsequent evaluation of ADI. The tissue distribution experiments showed that compared with a single dose of DOX, DOX and DOXol levels in the heart, kidney and liver were significantly increased after multiple doses of DOX, confirming the dose-dependent cardiotoxic effects of DOX.
Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress
Published in Drug and Chemical Toxicology, 2022
Eyup Altinoz, Zulal Oner, Hulya Elbe, Nuray Uremis, Muhammed Uremis
DOX, an antineoplastic drug from the anthracycline family, is used for a variety of neoplasms such as leukemias, lymphomas, and solid tumors. Nephrotoxicity is one of the most important side effects of anthracyclines. Although the mechanism of DOX is not fully understood, DOX causes intrarenal free radical production and changes kidney functions (Deman et al.2001, Öz and İlhan 2006). In the current study, we preferred the dose of DOX corresponds to the dose that is being used in clinical treatment (Chabner et al.2001). The dose of DOX in clinical practice for human (60 kg) is 74 mg/m2. Ajith et al. (2008) reported that single dose of DOX with ip injection caused acute kidney injury in rats that could be improved by Zingiber officinale. Yilmaz et al. (2006) showed that single dose of DOX administration (10 mg/kg) caused acute cardio-renal toxicity after 72 h. In this study, we aimed to investigate the effects of DOX on the kidney by biochemical and histopathological analyses.