Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 58, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2020.101769
Keywords
PAMAM dendrimers; In vitro drug delivery; Breast cancer therapy; Methotrexate; Chemotherapy
Categories
Funding
- Secretaria de Investigacion y Posgrado (SIP-IPN) [20140083, 20160665]
- Student Innovation project of Instituto Politecnico Nacional [201714]
- CONACyT
- BEIFI-IPN scholarship
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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 char-acterized by Fourier transform infrared spectroscopy, dynamic light scattering, and transmission electron mi-croscopy. 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 similar to 30 nm with a positive Z potential from similar to 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.
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