Mediating the Fate of Cancer Cell Uptake: Dual-Targeted Magnetic Nanovectors with Biotin and Folate Surface Ligands.
ACS Biomater Sci Eng
; 6(11): 6138-6147, 2020 11 09.
Article
em En
| MEDLINE
| ID: mdl-33449668
ABSTRACT
Recognition of folate and biotin surface receptors by dual-functionalized nanoparticles (NPs) is key for site-selective receptor-mediated transport of anticancer drugs to cancer cells. We present here dopamine-capped iron oxide nanoprobes (Fe3O4, 10 ± 2 nm) containing two surface-grafted biologically relevant ligands, namely, folic acid (FA) and biotin (BT). The covalent attachment of both FA and BT on Fe3O4 nanoparticles was achieved by following carbodiimide coupling and click-chemistry protocols. The dual-function Fe3O4 probes were delivered into E-G7 and human HeLa cancer cell lines and tested toward their cellular uptake by immunofluorescence and flow cytometry analysis. Owing to receptor-mediated endocytosis, enhanced accumulation of nanoprobes in cancer cells was successfully monitored by confocal laser microscopy. When compared to dual-function probes, single-functionalized nanoparticles possessing either FA or BT ligands showed significantly reduced uptake in the tested cell lines, underlining the superior interaction potential of dual-purpose probes. A time-dependent receptor-mediated endocytosis of FA-Fe3O4-BT nanovectors was demonstrated by flow cytometry analysis, whereas the unfunctionalized NPs did not show any specificity in terms of uptake. Besides their specific uptake, the surface-functionalized nanoparticles exhibited promising cytotoxicity profiles by demonstrating good viability of more than 95% with analogous cancer cell lines. Our results demonstrate that dual and/or multivariate conjugation of receptor-specific ligands on NPs is highly effective in molecular recognition of surface biomarkers that enhances their potential in anticancer treatment for pretargeting-radio strategies based on biotin/avidin interactions.
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Base de dados:
MEDLINE
Assunto principal:
Ácido Fólico
/
Neoplasias
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article