BODIPY-Mn nanoassemblies for accurate MRI and phototherapy of hypoxic cancer

Abstract

Hypoxia promotes not only the metastasis of tumors but also therapeutic resistance. Photosensitizer-mediated consumption of O₂ during photodynamic therapy (PDT) reinforces tumor hypoxia. Herein, a light-dependent attenuator of a hypoxic environment is reported for accurate MRI and phototherapy of hypoxic cancer. First, a photoresponsive Mn(II) nanoassembly was constructed, then it was assembled with bovine serum albumin (BSA) and modified with polyethylene glycol–folic acid (PEG–FA), forming cancer targeting Mn–DBA@BSA–FA nanoassemblies, which offer T₁ signals and can catalyze the water oxidation reaction under irradiation of red light emitting diode (LED) light with the generation of O₂ and heat. Moreover, they could selectively penetrate through and accumulate in the tumor tissues with clear T₁ magnetic resonance imaging (MRI) signals, and have remarkably eliminated the tumors in vivo, while they are of low toxicity to the healthy organs. The release of the Mn(II) complex from the nanoparticles in an acidic environment and the in vivo biodistribution results confirm the selective cancer targeting. Our work demonstrates the potential of nanoparticles as excellent theranostic agents for MR imaging combined with phototherapy triggered by near-infrared light.