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

被引：0

作者：

Barros, Mariana ^{[1
]}

Saez, Jose A. ^{[1
,2
]}

Arroyo, Pau ^{[1
,2
]}

Ros-Lis, J. Vicente ^{[1
]}

Garrido, M. Dolores ^{[3
]}

Martinez-Manez, Ramon ^{[1
,4
,5
,6
,7
]}

Terencio, M. Carmen ^{[1
,8
]}

Montesinos, M. Carmen ^{[1
,8
]}

Gavina, Pablo ^{[1
,2
,5
]}

机构：

[1] Univ Politecn Valencia, Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarro, C Doctor Moliner 50, Valencia 46100, Spain

[2] Univ Valencia, Dept Quim Organ, C Doctor Moliner 50, Valencia 46100, Spain

[3] Univ Valencia, Inst Ciencia dels Mat ICMUV, C Catedrat Jose Beltran 2, Valencia 46980, Spain

[4] Univ Politecn Valencia, Dept Quim, Camino Vera S-N, Valencia 46022, Spain

[5] Inst Salud Carlos III, CIBER Bioingn Biomat & Nanomed CIBER BBN, Madrid, Spain

[6] Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecanismos Enfermedad, C Eduardo Primo Yufera 3, Valencia 46100, Spain

[7] Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanit La Fe, Ave Fernando Abril Martorell 106, Valencia 46026, Spain

[8] Univ Valencia, Dept Farmacol, Ave Vicent Andres Estelles S-N, Valencia 46100, Spain

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2025年 / 672卷

关键词：

Hypoxia-responsive; Nitroreductase; Doxorubicin; Controlled delivery; Mesoporous silica nanocarriers; Self-immolative gatekeepers; TUMOR; CHEMOTHERAPY; CANCER;

D O I：

10.1016/j.ijpharm.2025.125326

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：10

共 31 条

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