Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells

Abstract Generation 4 of polyamidoamine dendrimer (G4-PAMAM) has several biological effects due to its tridimensional globular structure, repetitive branched amides, tertiary amines, and amino-terminal subunit groups liked to a common core. G4-PAMAM is cytotoxic due to its positive charges. However,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	R. Flores-Mejía, M. J. Fragoso-Vázquez, L. G. Pérez-Blas, A. Parra-Barrera, S. S. Hernández-Castro, A. R. Estrada-Pérez, J. Rodrígues, E. Lara-Padilla, A. Ortiz-Morales, J. Correa-Basurto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6e664926a0c04ffeb50ba5bbf7433697
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6e664926a0c04ffeb50ba5bbf7433697
record_format	dspace
spelling	oai:doaj.org-article:6e664926a0c04ffeb50ba5bbf74336972021-12-02T15:51:16ZChemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells10.1038/s41598-021-87560-w2045-2322https://doaj.org/article/6e664926a0c04ffeb50ba5bbf74336972021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87560-whttps://doaj.org/toc/2045-2322Abstract Generation 4 of polyamidoamine dendrimer (G4-PAMAM) has several biological effects due to its tridimensional globular structure, repetitive branched amides, tertiary amines, and amino-terminal subunit groups liked to a common core. G4-PAMAM is cytotoxic due to its positive charges. However, its cytotoxicity could increase in cancer cells due to the excessive intracellular negative charges in these cells. Furthermore, this work reports G4-PAMAM chemical structural characterization using UHPLC-QTOF-MS/MS (LC–MS) by electrospray ionization to measure its population according to its positive charges. Additionally, the antiproliferative effects and intracellular localization were explored in the HMC-1 and K-562 cell lines by confocal microscopy. The LC–MS results show that G4-PAMAM generated multivalent mass spectrum values, and its protonated terminal amino groups produced numerous positive charges, which allowed us to determine its exact mass despite having a high molecular weight. Additionally, G4-PAMAM showed antiproliferative activity in the HMC-1 tumor cell line after 24 h (IC50 = 16.97 µM), 48 h (IC50 = 7.02 µM) and 72 h (IC50 = 5.98 µM) and in the K-562 cell line after 24 h (IC50 = 15.14 µM), 48 h (IC50 = 14.18 µM) and 72 h (IC50 = 9.91 µM). Finally, our results showed that the G4-PAMAM dendrimers were located in the cytoplasm and nucleus in both tumor cell lines studied.R. Flores-MejíaM. J. Fragoso-VázquezL. G. Pérez-BlasA. Parra-BarreraS. S. Hernández-CastroA. R. Estrada-PérezJ. RodríguesE. Lara-PadillaA. Ortiz-MoralesJ. Correa-BasurtoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q R. Flores-Mejía M. J. Fragoso-Vázquez L. G. Pérez-Blas A. Parra-Barrera S. S. Hernández-Castro A. R. Estrada-Pérez J. Rodrígues E. Lara-Padilla A. Ortiz-Morales J. Correa-Basurto Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
description	Abstract Generation 4 of polyamidoamine dendrimer (G4-PAMAM) has several biological effects due to its tridimensional globular structure, repetitive branched amides, tertiary amines, and amino-terminal subunit groups liked to a common core. G4-PAMAM is cytotoxic due to its positive charges. However, its cytotoxicity could increase in cancer cells due to the excessive intracellular negative charges in these cells. Furthermore, this work reports G4-PAMAM chemical structural characterization using UHPLC-QTOF-MS/MS (LC–MS) by electrospray ionization to measure its population according to its positive charges. Additionally, the antiproliferative effects and intracellular localization were explored in the HMC-1 and K-562 cell lines by confocal microscopy. The LC–MS results show that G4-PAMAM generated multivalent mass spectrum values, and its protonated terminal amino groups produced numerous positive charges, which allowed us to determine its exact mass despite having a high molecular weight. Additionally, G4-PAMAM showed antiproliferative activity in the HMC-1 tumor cell line after 24 h (IC50 = 16.97 µM), 48 h (IC50 = 7.02 µM) and 72 h (IC50 = 5.98 µM) and in the K-562 cell line after 24 h (IC50 = 15.14 µM), 48 h (IC50 = 14.18 µM) and 72 h (IC50 = 9.91 µM). Finally, our results showed that the G4-PAMAM dendrimers were located in the cytoplasm and nucleus in both tumor cell lines studied.
format	article
author	R. Flores-Mejía M. J. Fragoso-Vázquez L. G. Pérez-Blas A. Parra-Barrera S. S. Hernández-Castro A. R. Estrada-Pérez J. Rodrígues E. Lara-Padilla A. Ortiz-Morales J. Correa-Basurto
author_facet	R. Flores-Mejía M. J. Fragoso-Vázquez L. G. Pérez-Blas A. Parra-Barrera S. S. Hernández-Castro A. R. Estrada-Pérez J. Rodrígues E. Lara-Padilla A. Ortiz-Morales J. Correa-Basurto
author_sort	R. Flores-Mejía
title	Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
title_short	Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
title_full	Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
title_fullStr	Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
title_full_unstemmed	Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells
title_sort	chemical characterization (lc–ms–esi), cytotoxic activity and intracellular localization of pamam g4 in leukemia cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6e664926a0c04ffeb50ba5bbf7433697
work_keys_str_mv	AT rfloresmejia chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT mjfragosovazquez chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT lgperezblas chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT aparrabarrera chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT sshernandezcastro chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT arestradaperez chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT jrodrigues chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT elarapadilla chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT aortizmorales chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells AT jcorreabasurto chemicalcharacterizationlcmsesicytotoxicactivityandintracellularlocalizationofpamamg4inleukemiacells
_version_	1718385638209748992

Chemical characterization (LC–MS–ESI), cytotoxic activity and intracellular localization of PAMAM G4 in leukemia cells

Ejemplares similares