Albumin-Based Nanotheranostic Probe with Hypoxia Alleviating Potentiates Synchronous Multimodal Imaging and Phototherapy for Glioma.

Abstract

Highly infiltrative and invasive glioma cells obscure the boundary between tumor and normal brain tissue, making it extremely difficult to precisely diagnose and completely remove. The combination of multimodal imaging with effective treatments to diagnose precisely and guide surgery and therapy accurately is desperately needed for glioma in the brain. Here, we report a biomimetic catalase-integrated-albumin phototheranostic nanoprobe (ICG/AuNR@BCNP) to realize multimodal imaging, amplify phototherapy, and guide surgery for glioma after penetrating the blood-brain barrier, accumulating into deep-seated glioma via albumin-binding protein mediated transportation. The phototheranostic nanoprobe enabled fluorescence, photoacoustic, and infrared thermal imaging with desirable detecting depth and high signal-to-background ratio for clearly differentiating brain tumors from surrounding tissues. Meanwhile, the nanoprobe could effectively induce local hyperthermia and promote the level of singlet oxygen based on alleviated hypoxic glioma microenvironment by decomposing endogenous hydrogen peroxide to oxygen to amplify phototherapy. Thus, significant inhibition of glioma growth, extended survival time, alleviated tumor hypoxia, improved apoptosis, and antiangiogenesis effects were exhibited in several animal models including the periphery and the brain through intravenous or intratumoral injection, meanwhile with low toxicity to normal tissue. The phototherapy was also guided by the assistance of external bioluminescence, magnetic resonance, and positron emission tomography imaging. Moreover, the nanoprobe could accurately guide the glioma resection. These results suggest that the phototheranostic nanoprobe is a promising nanoplatform specifically for glioma to achieve multimodal diagnosis, effective phototherapy, and accurate imaging-guided surgery.