TY - JOUR
T1 - Glycosylated one-step PAMAM dendrimers loaded with methotrexate for target therapy in breast cancer cells MDA-MB-231
AU - Torres-Pérez, Sergio Andrés
AU - Ramos-Godínez, María del Pilar
AU - Ramón-Gallegos, Eva
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8
Y1 - 2020/8
N2 - Polyamidoamine dendrimers (PAMAM) have been extensively investigated for drug delivery in target therapy against breast cancer and other diseases, but the development of a low-cost system — especially for triple-negative breast cancer (TNBC) — remains limited. The objective of this study was to evaluate the novel one-step PAMAM dendrimers loaded with methotrexate and D-glucose (OS-PAMAM-MTX-GLU) in TNBC cell lines, MDA-MB-231. The target drug system OS-PAMAM-MTX-GLU and control conjugates were synthesized and characterized by Fourier transform infrared spectroscopy, dynamic light scattering, and transmission electron microscopy. The in vitro viability of conjugates was studied by the MTT assay in TNBC cell line, MDA-MB-231 and non-cancerous HaCaT. Confocal and fluorescence microscopy were used to investigate the uptake time and colocalization of OS-PAMAM conjugates in cells. The results showed that OS-PAMAM-MTX-GLU and controls have the characteristic primary and secondary amides of PAMAM dendrimers, and the presence of MTX and GLU bound. Spherical dendrimeric conjugates of ∼30 nm with a positive Z potential from ∼13 to 19 mV were found. The OS-PAMAM-MTX-GLU reduces the cell viability up to 20% mostly MDA-MB-231 cells and is significantly higher than free MTX without affecting significantly HaCaT cells. The uptake studies showed that glycosylation increased two times the internalization of OS-PAMAM conjugates in cancer cells than non-cancer cells. The OS-PAMAM-MTX-GLU uptake inhibits mostly MDA-MB-231 cells providing a desirable strategy for targeted therapy of breast cancer cells.
AB - Polyamidoamine dendrimers (PAMAM) have been extensively investigated for drug delivery in target therapy against breast cancer and other diseases, but the development of a low-cost system — especially for triple-negative breast cancer (TNBC) — remains limited. The objective of this study was to evaluate the novel one-step PAMAM dendrimers loaded with methotrexate and D-glucose (OS-PAMAM-MTX-GLU) in TNBC cell lines, MDA-MB-231. The target drug system OS-PAMAM-MTX-GLU and control conjugates were synthesized and characterized by Fourier transform infrared spectroscopy, dynamic light scattering, and transmission electron microscopy. The in vitro viability of conjugates was studied by the MTT assay in TNBC cell line, MDA-MB-231 and non-cancerous HaCaT. Confocal and fluorescence microscopy were used to investigate the uptake time and colocalization of OS-PAMAM conjugates in cells. The results showed that OS-PAMAM-MTX-GLU and controls have the characteristic primary and secondary amides of PAMAM dendrimers, and the presence of MTX and GLU bound. Spherical dendrimeric conjugates of ∼30 nm with a positive Z potential from ∼13 to 19 mV were found. The OS-PAMAM-MTX-GLU reduces the cell viability up to 20% mostly MDA-MB-231 cells and is significantly higher than free MTX without affecting significantly HaCaT cells. The uptake studies showed that glycosylation increased two times the internalization of OS-PAMAM conjugates in cancer cells than non-cancer cells. The OS-PAMAM-MTX-GLU uptake inhibits mostly MDA-MB-231 cells providing a desirable strategy for targeted therapy of breast cancer cells.
KW - Breast cancer therapy
KW - Chemotherapy
KW - In vitro drug delivery
KW - Methotrexate
KW - PAMAM dendrimers
UR - http://www.scopus.com/inward/record.url?scp=85087130038&partnerID=8YFLogxK
U2 - 10.1016/j.jddst.2020.101769
DO - 10.1016/j.jddst.2020.101769
M3 - Artículo
SN - 1773-2247
VL - 58
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
M1 - 101769
ER -