Monitoring the subcellular localization of doxorubicin in CHO-K1 using MEKC−LIF: Liposomal carrier for enhanced drug delivery

Ho, Ja‐an Annie; Fan, Nien-Chu; Jou, Amily Fang-Ju; Wu, Li-Chen; Sun, Tai‐Ping

doi:10.1016/j.talanta.2012.06.077

Cited by 20 publications

(16 citation statements)

References 41 publications

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“…DOX fluorescence intensity in sensitive cells increased proportionally to the increase in incubation time, whereas in resistant cells the fluorescence intensity was at a similar, constant level. Similar research results were obtained by other research groups [52,53]. The analysis of the distribution and elimination of DOX from the cells was performed in tests with and without the application of electrical impulses.…”

Section: Discussionsupporting

confidence: 69%

Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

et al. 2020

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Electroporation increases the transmembrane transport of molecules. The combination of electric pulses with cytostatic compounds is beneficial for cancer treatment. Doxorubicin (DOX) is a commonly used chemotherapeutic anticancer drug. Its fluorescence properties enable the investigation of drug distribution and metabolism. In this study, doxorubicin was enhanced by electroporation to eliminate cancer cells more effectively. The influence of electroporation on the drug uptake was evaluated in two cell lines: MCF-7/WT and MCF-7/DOX. The intracellular localization of doxorubicin and its impact on the intracellular structure organization were examined under a confocal microscope. Cellular effects were examined with the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test that estimates the rate of metabolism in viable cells. The ultrastructure (TEM) of tumor cells subjected to the electric field was analyzed. An enhanced doxorubicin efficacy was observed in MCF-7/DOX cells after combination with electroporation. The response of the resistant cell line was revealed to be more sensitive to electric pulses. Electroporation-based methods may be attractive for cancer treatment in human breast adenocarcinoma, especially with acquired resistance. Electroporation enables a reduction of the effective dose of the drugs and the exposure time in this type of cancer, diminishing side effects of the systemic therapy.

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Section: Discussionsupporting

confidence: 69%

Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

et al. 2020

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“…44 DOX intercalates into DNA, causing DNA damage and disrupting the replication and transcription processes. Meanwhile, DOX is able to inhibit topoisomerase II, leading to cell death.…”

Section: Cell-death Mechanismmentioning

confidence: 99%

Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

Zheng¹,

Li²,

Zhou³

et al. 2015

IJN

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Doxorubicin (DOX) is an effective chemotherapy drug used to treat different types of cancers. However, DOX has severe side effects, especially life-threatening cardiotoxicity. We herein report a new approach to reduce the toxicity of DOX by embedding DOX inside human serum albumin (HSA). HSA is further fused by a molecular biology technique with a tumor-targeting agent, amino-terminal fragment of urokinase (ATF). ATF binds with a high affinity to urokinase receptor, which is a cell-surface receptor overexpressed in many types of tumors. The as-prepared macromolecule complex (ATF–HSA:DOX) was not as cytotoxic as free DOX to cells in vitro, and was mainly localized in cell cytosol in contrast to DOX that was localized in cell nuclei. However, in tumor-bearing mice, ATF–HSA:DOX was demonstrated to have an enhanced tumor-targeting and antitumor efficacy compared with free DOX. More importantly, histopathological examinations of the hearts from the mice treated with ATF–HSA:DOX showed a significantly reduced cardiotoxicity compared with hearts from mice treated with free DOX. These results demonstrate the feasibility of this approach in reducing the cardiotoxicity of DOX while strengthening its antitumor efficacy. Such a tumor-targeted albumin packaging strategy can also be applied to other antitumor drugs.

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“…Doxorubicin (DOX), an anthracycline glycoside antibiotic, is an exceptionally good antineoplastic agent and is widely used in the treatment of various cancers, including lung, ovarian and breast cancer and malignant lymphoma (Duggan & Keating, 2011). However, long-term clinical use is limited due to the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure (Ho, Fan, Jou, Wu, & Sun, 2012). The current thinking is that DOX is toxic per se but gains further cardiotoxicity after one-electron reduction with reactive oxygen species overproduction or two-electron reduction with conversion to a secondary alcohol metabolite doxorubicinol (DOXol).…”

Section: Introductionmentioning

confidence: 99%

LC–MS/MS method development for quantification of doxorubicin and its metabolite 13‐hydroxy doxorubicin in mice biological matrices: Application to a pharmaco‐delivery study

Mazzucchelli

Ravelli

Gigli

et al. 2016

Biomedical Chromatography

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This study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5-250 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in plasma and tumor, over the range 25-500 ng/mL for doxorubicin and 1.25-25 ng/mL for doxorubicinol in liver and kidney, and over the range 25-1000 ng/mL for doxorubicin and doxorubicinol in urine. The study was validated, using quality control samples prepared in all different matrices, for accuracy, precision, linearity, selectivity, lower limit of quantification and recovery in accordance with the US Food & Drug Administration guidelines. The method was successfully applied in determining the pharmaco-distribution of doxorubicin and doxorubicinol after intravenously administration in tumor-bearing mice of drug, free or nano-formulated in ferritin nanoparticles or in liposomes. Obtained results demonstrate an effective different distribution and doxorubicin protection against metabolism linked to nano-formulation. This method, thanks to its validation in plasma and urine, could be a powerful tool for pharmaceutical research and therapeutic drug monitoring, which is a clinical approach currently used in the optimization of oncologic treatments.

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Monitoring the subcellular localization of doxorubicin in CHO-K1 using MEKC−LIF: Liposomal carrier for enhanced drug delivery

Cited by 20 publications

References 41 publications

Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

LC–MS/MS method development for quantification of doxorubicin and its metabolite 13‐hydroxy doxorubicin in mice biological matrices: Application to a pharmaco‐delivery study

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