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Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy

Fecha de publicación:

Autores de CIPF

Participantes ajenos a CIPF

  • Vivo-Llorca, G
  • Morella-Aucejo, A
  • Garcia-Fernandez, A
  • Diez, P
  • Llopis-Lorente, A
  • Martinez-Manez, R

Grupos de Investigación

Abstract

Introduction: Breast cancer has the highest mortality rate among cancers in women. Patients suffering from certain breast cancers, such as triple-negative breast cancer (TNBC), lack effective treatments. This represents a clinical concern due to the associated poor prognosis and high mortality. As an approach to succeed over conventional therapy limitations, we present herein the design and evaluation of a novel nanodevice based on enzyme-functionalized gold nanoparticles to efficiently perform enzyme prodrug therapy (EPT) in breast cancer cells. Results: In particular, the enzyme horseradish peroxidase (HRP) - which oxidizes the prodrug indole-3-acetic acid (IAA) to release toxic oxidative species - is incorporated on gold nanoconjugates (HRP-AuNCs), obtaining an efficient nanoplatform for EPT. The nanodevice is biocompatible and effectively internalized by breast cancer cell lines. Remarkably, co-treatment with HRP-AuNCs and IAA (HRP-AuNCs/IAA) reduces the viability of breast cancer cells below 5%. Interestingly, 3D tumor models (multicellular tumor spheroid-like cultures) co-treated with HRP-AuNCs/IAA exhibit a 74% reduction of cell viability, whereas the free formulated components (HRP, IAA) have no effect. Conclusion: Altogether, our results demonstrate that the designed HRP-AuNCs nanoformulation shows a remarkable therapeutic performance. These findings might help to bypass the clinical limitations of current tumor enzyme therapies and advance towards the use of nanoformulations for EPT in breast cancer. prodrug therapy, breast cancer

Datos de la publicación

ISSN/ISSNe:
1178-2013, 1176-9114

International Journal of Nanomedicine  Dove Medical Press Ltd

Tipo:
Article
Páginas:
409-422
PubMed:
35115775

Citas Recibidas en Web of Science: 10

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Métricas

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Keywords

  • gold nanoconjugates; horseradish peroxidase; indole-3-acetic acid; enzyme

Campos de Estudio

Financiación

European Social Fund (CD20/00120)
European Unions Horizon 2020 research and innovation programme (847675)
Generalitat Valenciana (ACIF/2017/072)
Generalitat Valenciana (APOSTD/2020/153)
Generalitat Valenciana (PROMETEO/2018/024)
Generalitat Valenciana (PROMETEO/2019/065)
Instituto de Salud Carlos III (CD20/00120)
Spanish Government (RTI2018-100910-B-C41)
Spanish Government (SAF2017-84689-R-B)

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