A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia.

ABSTRACT: Vascular-targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)-based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxia-activated prodrug (HAP), and HIF-1α siRNA (siHIF-1α) (3) is reported. The VTP-induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a topoisomerase II inhibitor) for chemotherapy. However, the hypoxia-induced HIF-1α acts as a "hidden brake," through downregulating CYP450 (the dominant HAP-activating reductases), to s

SUBMITTER: Luan X 

PROVIDER: S-EPMC6097144 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature