RT Journal Article
T1 Tunable gold nanorod/NAO conjugates for selective drug delivery in mitochondria-targeted cancer therapy
A1 González-Rubio, Sergio
A1 Cástor, Salgado
A1 Manzaneda González, Vanesa
A1 Muñoz Úbeda, Mónica
A1 Ahijado Guzmán, Rubén
A1 Natale, Paolo
A1 Almendro Vedia, Víctor Galileo
A1 Junquera González, María Elena
A1 Osío Barcina, José De Jesús
A1 Ferrer, Irene
A1 Guerrero Martínez, Andrés
A1 Paz-Ares, Luz
A1 López Montero, Iván
AB Nonyl acridine orange (NAO) is a lipophilic and positively charged molecule widely used as a mitochondrial fluorescent probe. NAO is cytotoxic at micromolar concentration and might be potentially used as a mitochondria-targeted drug for cancer therapy. However, the use of NAO under in vivo conditions would be compromised by the unspecific interactions with off-target cells and negatively charged proteins present in the bloodstream. To tackle this limitation, we have synthesized NAO analogues carrying an imidazole group for their specific binding to nitrilotriacetic (NTA) functionalized gold nanorods (AuNRs). We demonstrate that AuNRs provide 104 binding sites and a controlled delivery under acidic conditions. Upon incubation with mouse embryonic fibroblasts, the endosomal acidic environment releases the NAO analogues from AuNRs, as visualized through the staining of the mitochondrial network. The addition of the monoclonal antibody Cetuximab to the conjugates enhanced their uptake within lung cancer cells and the conjugates were cytotoxic at subnanomolar concentrations (c50 ≈ 0.06 nM). Moreover, the specific interactions of Cetuximab with the epidermal growth factor receptor (EGFR) provided a specific targeting of EGFR-expressing lung cancer cells.  After intravenous administration in patient-derived xenografts (PDX) mouse models, the conjugates reduced the progression of EGFR-positive tumors. Overall, the NAO-AuNRs provide a promising strategy to realize membrane mitochondria-targeted conjugates for lung cancer therapy.
SN 2040-3372
YR 2022
FD 2022
LK https://hdl.handle.net/20.500.14352/108993
UL https://hdl.handle.net/20.500.14352/108993
LA eng
NO González-Rubio S, Salgado C, Manzaneda-González V, Muñoz-Úbeda M, Ahijado-Guzmán R, Natale P, et al. Tunable gold nanorod/NAO conjugates for selective drug delivery in mitochondria-targeted cancer therapy. Nanoscale 2022;14:8028–40. https://doi.org/10.1039/D2NR02353A.
NO Consejo Europeo de Investigación (ERC)
NO Ministerio de Ciencia, Innovación y Universidades
NO Comunidad Autónoma de Madrid
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 8 abr 2025