MUC1 Aptamer-Capped Mesoporous Silica Nanoparticles for Navitoclax Resistance Overcoming in Triple-Negative Breast Cancer
Por:
G. VIVO-LLORCA, V. CANDELA-NOGUERA, M. ALFONSO, A. GARCIA-FERNANDEZ, M. ORZAEZ, F. SANCENON and R. MARTINEZ-MANEZ
Publicada:
9 dic 2020
Ahead of Print:
1 oct 2020
Resumen:
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. In the last years, navitoclax has emerged as a possible treatment for TNBC. Nevertheless, rapid navitoclax resistance onset has been observed thorough Mcl-1 overexpression. As a strategy to overcome Mcl-1-mediated resistance, herein we present a controlled drug co-delivery system based on mesoporous silica nanoparticles (MSNs) targeted to TNBC cells. The nanocarrier is loaded with navitoclax and the Mcl-1 inhibitor S63845 and capped with a MUC1-targeting aptamer (apMUC1-MSNs(Nav/S63845)). The apMUC1-capped nanoparticles effectively target TNBC cell lines and successfully induce apoptosis, overcoming navitoclax resistance. Moreover, navitoclax encapsulation protects platelets against apoptosis. These results point apMUC1-gated MSNs as suitable BH3 mimetics nanocarriers in the targeted treatment of MUC1-expressing TNBC.
Filiaciones:
:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
Univ Politecn Valencia, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain
Ctr Invest Principe Felipe, Eduardo Primo Yufera 3, Valencia 46012, Spain
V. CANDELA-NOGUERA:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
M. ALFONSO:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid, Spain
Univ Politecn Valencia, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain
Ctr Invest Principe Felipe, Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Univ Politecn Valencia, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain
Ctr Invest Principe Felipe, Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid, Spain
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, IIS La Fe, Valencia, Spain
Univ Politecn Valencia, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain
Ctr Invest Principe Felipe, Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Valencia, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid, Spain
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, IIS La Fe, Valencia, Spain
Univ Politecn Valencia, Unidad Mixta UPV CIPF Invest Mecanismos Enfermeda, Valencia, Spain
Ctr Invest Principe Felipe, Eduardo Primo Yufera 3, Valencia 46012, Spain
|