Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
Por:
J. ESTEVE-MORENO, A. ESCUDERO, O. SILVESTRE, J. TERRÉS, M. GORBE, E. GARRIDO, C. RENERO-LECUNA, J. LANGER, M. ALFONSO, J. IBAÑEZ, F. SANCENÓN, R. CAO-MILÁN, L. LIZ-MARZÁN, A. GARCÍA-FERNÁNDEZ, A. HERNÁNDEZ-MONTOTO and R. MARTÍNEZ-MÁÑEZ
Publicada:
9 sep 2025
Ahead of Print:
1 sep 2025
Resumen:
Bioorthogonal chemistry that can be controlled through near-infrared (NIR) light is a promising route to therapeutics. This study proposes a method to intracellularly photoactivate prodrugs using plasmonic gold nanostars (AuNSt) and NIR irradiation. Two strategies are followed. On one hand, doxorubicin (Dox) masked with a 2-nitrobenzyl carbamate (proDox1) is used as a photoactivatable prodrug. In the second strategy, a photolabile Dox prodrug (proDox2) obtained by modification of Dox with 2-nitrobenzyl diol bearing a disulfide is attached to the AuNSt surface. Under NIR irradiation AuNSt induce local electromagnetic field enhancement, leading to photocleavage of the 2-nitrobenzyl moiety in both proDox1 and proDox2, and subsequent Dox release. Near field enhancement by excitation of surface plasmons in AuNSt is sufficient to record the surface-enhanced Raman scattering (SERS) spectra of proDox1 and proDox2. The therapeutic potential of this bioorthogonal photoactivation strategy is confirmed in vitro and in vivo using a mouse model of human melanoma. NIR-activated AuNSt induce in vivo the intracellular release of Dox and subsequent cancer cell death, thus reducing tumor growth at low irradiation power density to avoid undesired photothermal effects. These results demonstrate that AuNSt are suitable platforms for NIR light-triggered drug delivery in cancer therapy.
Filiaciones:
J. ESTEVE-MORENO:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
O. SILVESTRE:
Basque Res & Technol Alliance BRTA, CIC BiomaGUNE, Paseo Miramon 194, Donostia San Sebastian 20014, Spain
Univ Otago, Sch Pharm, Dunedin 9016, New Zealand
J. TERRÉS:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
M. GORBE:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
E. GARRIDO:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
C. RENERO-LECUNA:
Basque Res & Technol Alliance BRTA, CIC BiomaGUNE, Paseo Miramon 194, Donostia San Sebastian 20014, Spain
Univ Vigo, CINBIO, Vigo 36310, Spain
J. LANGER:
Basque Res & Technol Alliance BRTA, CIC BiomaGUNE, Paseo Miramon 194, Donostia San Sebastian 20014, Spain
M. ALFONSO:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
J. IBAÑEZ:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
F. SANCENÓN:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe, Ave Fernando Abril Martorell, Torre 106 7planta, Valencia 46026, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
R. CAO-MILÁN:
Univ La Habana, Fac Quim, Havana 10400, Cuba
L. LIZ-MARZÁN:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Basque Res & Technol Alliance BRTA, CIC BiomaGUNE, Paseo Miramon 194, Donostia San Sebastian 20014, Spain
Ikerbasque, Bilbao 48009, Spain
:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
A. HERNÁNDEZ-MONTOTO:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe, Ave Fernando Abril Martorell, Torre 106 7planta, Valencia 46026, Spain
:
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, Camino Vera S-N, Valencia 46022, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid 28040, Spain
Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46012, Spain
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe, Ave Fernando Abril Martorell, Torre 106 7planta, Valencia 46026, Spain
Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain
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