DNA is an excellent programmable polymer for the generation of self-assembled multivalent nanostructures useful for biomedical applications. Herein, we developed (i) folate-functionalized nanocages (Fol-NC), very efficiently internalized by tumor cells overexpressing the alpha isoform of the folate receptor; (ii) AS1411-linked nanocages (Apt-NC), internalized through nucleolin, a protein overexpressed in the cell surface of many types of cancers; and (iii) nanostructures that harbor both folate and AS1411 aptamer functionalization (Fol-Apt-NC). We analyzed the specific miRNA silencing activity of all types of nanostructures harboring miRNA sequestering sequences complementary to miR-21 and the cytotoxic effect when loaded with doxorubicin in a drug-resistant triple-negative breast cancer cell line. We demonstrate that the presence of folate as a targeting ligand increases the efficiency in miR-21 silencing compared to nanocages functionalized with AS1411. Double-functionalized nanocages (Fol-Apt-NC), loaded with doxorubicin, resulted in an increase of over 51% of the cytotoxic effect on MDA-MB-231 cells compared to free doxorubicin, demonstrating, besides selectivity, the ability of nanocages to overcome Dox chemoresistance. The higher efficiency of the folate-functionalized nanocages is due to the way of entrance, which induces more than four times higher intracellular stability and indicates that the folate-mediated route of cell entry is more efficient than the nucleolin-mediated one when both folate and AS1411 modifications are present.

Unida, V., Vindigni, G., Raniolo, S., Stolfi, C., Desideri, A., Biocca, S. (2022). Folate-Functionalization Enhances Cytotoxicity of Multivalent DNA Nanocages on Triple-Negative Breast Cancer Cells. PHARMACEUTICS, 14(12), 2610 [10.3390/pharmaceutics14122610].

Folate-Functionalization Enhances Cytotoxicity of Multivalent DNA Nanocages on Triple-Negative Breast Cancer Cells

Unida V.;Vindigni G.;Raniolo S.;Stolfi C.;Desideri A.;Biocca S.
Conceptualization
2022-11-26

Abstract

DNA is an excellent programmable polymer for the generation of self-assembled multivalent nanostructures useful for biomedical applications. Herein, we developed (i) folate-functionalized nanocages (Fol-NC), very efficiently internalized by tumor cells overexpressing the alpha isoform of the folate receptor; (ii) AS1411-linked nanocages (Apt-NC), internalized through nucleolin, a protein overexpressed in the cell surface of many types of cancers; and (iii) nanostructures that harbor both folate and AS1411 aptamer functionalization (Fol-Apt-NC). We analyzed the specific miRNA silencing activity of all types of nanostructures harboring miRNA sequestering sequences complementary to miR-21 and the cytotoxic effect when loaded with doxorubicin in a drug-resistant triple-negative breast cancer cell line. We demonstrate that the presence of folate as a targeting ligand increases the efficiency in miR-21 silencing compared to nanocages functionalized with AS1411. Double-functionalized nanocages (Fol-Apt-NC), loaded with doxorubicin, resulted in an increase of over 51% of the cytotoxic effect on MDA-MB-231 cells compared to free doxorubicin, demonstrating, besides selectivity, the ability of nanocages to overcome Dox chemoresistance. The higher efficiency of the folate-functionalized nanocages is due to the way of entrance, which induces more than four times higher intracellular stability and indicates that the folate-mediated route of cell entry is more efficient than the nucleolin-mediated one when both folate and AS1411 modifications are present.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/12
English
AS1411
DNA nanostructure
doxorubicin delivery
folate receptor
miR-21
nucleolin
Unida, V., Vindigni, G., Raniolo, S., Stolfi, C., Desideri, A., Biocca, S. (2022). Folate-Functionalization Enhances Cytotoxicity of Multivalent DNA Nanocages on Triple-Negative Breast Cancer Cells. PHARMACEUTICS, 14(12), 2610 [10.3390/pharmaceutics14122610].
Unida, V; Vindigni, G; Raniolo, S; Stolfi, C; Desideri, A; Biocca, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/311837
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