Light-triggered hypoxia-responsive nanoscale metal-organic frameworks for highly efficient antitumor treatment

Abstract

Photodynamic therapy (PDT), as a noninvasive therapeutic tool, can result in a high level of hypoxia in tumors. Herein, hypoxia-responsive nanoscale metal-organic frameworks (UiO-AZB) are prepared, which contain an azo group in its organic linker. After modifying the surface of UiO-AZB with chlorin e6 (Ce6)-conjugated human serum albumin (HSA), tirapazamine (TPZ) is employed as a hypoxia-activated prodrug to be encapsulated into UiO-AZB. The obtained nanosystem (UiO-AZB/HC-TPZ) can efficiently produce singlet oxygen under 660 nm light irradiation and cause severe hypoxia in tumors. This process in turn triggers the degradation of the frameworks and controllable release of activated TPZ for chemotherapy, finally leading to improved antitumor treatment through combinational PDT and hypoxia-activated chemotherapy. This research demonstrates a distinctive treatment strategy, that is, using a simple stimulus (light irradiation) to trigger a series of activities (PDT, disintegration of UiO-AZB structure, activation of TPZ, and controllable release) for realizing an effective treatment of tumors.