Screening of Polymer-Based Drug Delivery Vehicles Targeting Folate Receptors in Triple-Negative Breast Cancer.
J Vasc Interv Radiol
; 31(11): 1866-1873.e2, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-33129432
ABSTRACT
PURPOSE:
To compare cellular uptake and cytotoxicity of fluorescein (FL)-labeled polyethylene glycols (PEGs) carrying 2 folate groups (targeted delivery vehicles [TDVs]) to non-PEGylated molecules with 1 or 2 folate groups. MATERIALS ANDMETHODS:
Three PEGylated TDVs and 2 non-PEGylated folic acid (FA)-fluorescein (FL) conjugates (FA-FL and FA-FL-FA) were synthesized. Two triple-negative breast cancer cell lines (MDA-MB-231and MDA-MB-468) were cultured to 70% confluency and incubated for 2 h in a folate-depleted medium. Folate receptor (FR) expression was confirmed by immunocytochemistry. Cellular uptake and cytotoxicity of compounds were measured by flow cytometry. Intracellular localization was confirmed using confocal microscopy.RESULTS:
MDA-MB-231 demonstrated 40% more FR staining than MD-MB-468. Intracellular localization of the 2 non-PEGylated molecules (FA-FL and FA-FL-FA) and the 3 PEGylated TDVs was confirmed with confocal microscopy. Cellular uptake was independent of concentration for FA-FL, but there was 26.8% more cytotoxicity at 30 µg/mL compared with no treatment (P ≤ .05). Uptake was > 90% for FA-FL-FA at 10 µg/mL and 30 µg/mL without significant cytotoxicity (P ≤ .005). Cellular uptake was > 80% for all TDVs. The molecule containing monodispersed PEG with Mn = 1,000 g/mol had the highest uptake in both cell lines without cytotoxicity. Maximum toxicity was demonstrated by the molecule containing PEG2,000 only at the highest dose of 30 µg/mL (8.66% ± 3.94% cytotoxicity; cut-off was 20%).CONCLUSIONS:
The molecule containing monodispersed PEG with Mn = 1,000 g/mol and 2 FA targeting groups demonstrated better targetability and cellular uptake as a TDV.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Portadores de Fármacos
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Neoplasias de Mama Triplo Negativas
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Ácido Fólico
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article