Dataset Information

Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application.

ABSTRACT: Breast cancer is a major global health problem with high incidence and case fatality rates. The use of magnetoliposomes has been suggested as an effective therapeutic approach because of their good specificity for cancers. In this study, we developed two novel magnetoliposomes, namely, Gemcitabine-containing magnetoliposome (GML) and Oxaliplatin-containing magnetoliposome (OML). These magnetoliposomes were combined (CGOML) was used to treat breast cancer under an external magnetic field. Biosafety test results showed that GML and OML were biologically safe to blood cells and did not adversely affect the behavior of mice. Pharmacokinetic and tissue distribution studies indicated that both magnetoliposomes exhibited stable structures and persisted at the target area under an external magnetic field. Cell and animal experiments revealed that CGOML can markedly suppress the growth of MCF-7 cells, and only the CGOML group can minimize the tumor size among all the groups. Finally, CGOML can significantly inhibit MCF-7cell growth both in vitro and vivo by activating the apoptotic signaling pathway of MCF-7 cells.

SUBMITTER: Ye H

PROVIDER: S-EPMC5190058 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application.

Ye Hui H Tong Jiansong J Liu Jiangyi J Lin Wenman W Zhang Chengshou C Chen Kai K Zhao Jie J Zhu Wenjing W

Oncotarget 20160701 28

Breast cancer is a major global health problem with high incidence and case fatality rates. The use of magnetoliposomes has been suggested as an effective therapeutic approach because of their good specificity for cancers. In this study, we developed two novel magnetoliposomes, namely, Gemcitabine-containing magnetoliposome (GML) and Oxaliplatin-containing magnetoliposome (OML). These magnetoliposomes were combined (CGOML) was used to treat breast cancer under an external magnetic field. Biosafe ...[more]

PMID: 27248325

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Project description:Early diagnosis, intervention, and therapeutic advancements have extended the lives of breast cancer patients; however, even with molecularly targeted therapies, many patients eventually progress to metastatic cancer. Recent data suggest that residual breast cancer cells often reside in the lymphatic system before rapidly spreading through the bloodstream. To address this challenge, an effective drug combination composed of gemcitabine (G) and paclitaxel (T) is administered intravenously in sequence at the metastatic stage, but intravenous GT infusion may limit lymphatic GT drug accessibility and asynchronous drug exposure in cancer cells within the lymph. To determine whether co-localization of intracellular gemcitabine and paclitaxel (referred to as GT) could overcome these limitations and enhance the efficacy of GT, we have evaluated a previously reported GT drug-combination formulated in nanoparticle (referred to as GT-in-DcNP) evaluated in an orthotopic breast tumor model. Previously, with indocyanine green-labeled nanoparticles, we reported that GT-in-DcNP particles after subcutaneous dosing were taken up rapidly and preferentially into the lymph instead of blood vessels. The pharmacokinetic study showed enhanced co-localization of GT within the tumors and likely through lymphatic access, before drug apparency in the plasma leading to apparent long-acting plasma time-course. The mechanisms may be related to significantly greater inhibitions of tumor growth-by 100 to 140 times-in both sub-iliac and axillary regions compared to the equivalent dosing with free-and-soluble GT formulation. Furthermore, GT-in-DcNP exhibited dose-dependent effects with significant tumor regression. In contrast, even at the highest dose of free GT combination, only a modest tumor growth reduction was notable. Preliminary studies with MDA-231-HM human breast cancer in an orthotopic xenograft model indicated that GT-in-DcNP may be effective in suppressing human breast tumor growth. Taken together, the synchronized delivery of GT-in-DcNP to mammary tumors through the lymphatic system offers enhanced cellular retention and greater efficacy.

Dataset Information

Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application.

Publications

Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application.

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