Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery

Autores de IIS La Fe

• Ramón Martínez Máñez

  Autor

Participantes ajenos a IIS La Fe

• Barros, Mariana
• Saez, Jose A.
• Arroyo, Pau
• Ros-Lis, J. Vicente
• Garrido, M. Dolores
• Terencio, M. Carmen
• Montesinos, M. Carmen
• Gavina, Pablo

Grupos

• Unidad Mixta de Investigación en Nanomedicina y Sensores

  Leader

  Ramón Martínez Máñez

Abstract

Hypoxia, i.e., low oxygen concentration at the tissue level, is a common feature of most solid tumors, and is responsible for their enhanced aggressiveness and resistance to chemotherapy, radiotherapy and photodynamic therapy. Hypoxic microenvironments are also characterized by the overexpression of various reductase enzymes such as nitroreductases. Herein, we report a hypoxia-responsive hybrid nanomaterial consisting of mesoporous silica nanoparticles, loaded with the chemotherapy drug doxorubicin, and functionalized on their surface with a self-immolative gatekeeper responsive to nitroreductases, for the controlled release of the cargo. Thus, under bioreductive conditions, elicited by the presence of nitroreductase and NADH, the reduction of the nitroaromatic containing molecular gate induces a self-immolative elimination leading to the disintegration of the gatekeeper and the delivery of the doxorubicin from inside the pores. The nitroreductase-responsive nanocarrier has been tested in vitro with A549 cells, that are known to express nitroreductase, to demonstrate its effectiveness as drug carrier for doxorubicin release, showing great potential for the treatment of hypoxic tumors.