Targeted Lipid Nanoemulsions Encapsulating Epigenetic Drugs Exhibit Selective Cytotoxicity on CDH1<sup>-</sup>/FOXM1<sup>+</sup> Triple Negative Breast Cancer Cells.

Kim, Bumjun; Pena, Caroline D; Auguste, Debra T

Targeted Lipid Nanoemulsions Encapsulating Epigenetic Drugs Exhibit Selective Cytotoxicity on CDH1^-/FOXM1⁺ Triple Negative Breast Cancer Cells.

Kim, Bumjun; Pena, Caroline D; Auguste, Debra T.

Afiliación

Kim B; Department of Biomedical Engineering , The City College of New York , 160 Convent Avenue , New York , New York 10031 , United States.
Pena CD; Department of Biomedical Engineering , The City College of New York , 160 Convent Avenue , New York , New York 10031 , United States.
Auguste DT; Department of Biomedical Engineering , The City College of New York , 160 Convent Avenue , New York , New York 10031 , United States.

Mol Pharm ; 16(5): 1813-1826, 2019 05 06.

Article en En | MEDLINE | ID: mdl-30883132

RESUMEN

The plasticity of cancer epigenetics makes them plausible candidates for therapeutic intervention. We took advantage of elevated expression of lysophosphatidic acid receptor 1 (LPAR1) in triple negative breast cancer (TNBC) tissues to target decitabine (DAC) and panobinostat (PAN) to breast cancer cells. DAC and PAN were shown to reverse abnormal methylation of DNA and altered chromatin structure, respectively, leading to increased expression of tumor suppressor genes and decreased expression of oncogenes. Although DAC and PAN have therapeutic benefits, they are limited by chemical instability and systemic toxicity. Herein, we present LPAR1-targeted, lipid nanoemulsions (LNEs) encapsulating both DAC and PAN. Our results demonstrated that the cell uptake and in vivo biodistribution of LNEs was dependent on LPAR1 expression in TNBCs. DAC/PAN-LNEs were effective in inhibiting the growth of mesenchymal breast cancer cells by restoring CDH1/E-cadherin and suppressing forkhead box M1 (FOXM1) expression. Epithelial breast cancer cells that inherently express low FOXM1 and high CDH1 were unaffected by DAC/PAN-LNEs. Overall, we successfully designed LPAR1-targeted LNEs that selectively act on CDH1(low)/FOXM1(high) TNBC cell lines.

Asunto(s)

Antígenos CD/metabolismo; Antimetabolitos Antineoplásicos/farmacocinética; Cadherinas/metabolismo; Decitabina/farmacocinética; Proteína Forkhead Box M1/metabolismo; Lípidos/química; Nanocápsulas/química; Panobinostat/farmacocinética; Neoplasias de la Mama Triple Negativas/tratamiento farmacológico; Animales; Antimetabolitos Antineoplásicos/uso terapéutico; Proliferación Celular/efectos de los fármacos; Decitabina/uso terapéutico; Diseño de Fármacos; Liberación de Fármacos; Estabilidad de Medicamentos; Femenino; Xenoinjertos; Células Endoteliales de la Vena Umbilical Humana; Humanos; Células MCF-7; Ratones; Ratones Desnudos; Panobinostat/uso terapéutico; Receptores del Ácido Lisofosfatídico/metabolismo; Transducción de Señal/efectos de los fármacos; Distribución Tisular; Neoplasias de la Mama Triple Negativas/patología

Palabras clave

CDH1; FOXM1; LPA, LPAR1; decitabine; epigenetic; lipid nanoemulsion; panobinostat; triple negative breast cancer

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos CD / Cadherinas / Nanocápsulas / Neoplasias de la Mama Triple Negativas / Proteína Forkhead Box M1 / Decitabina / Panobinostat / Lípidos / Antimetabolitos Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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