Near-Infrared Photoimmunotherapy in Brain Tumors-An Unexplored Frontier

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer treatment that uses near-infrared light to activate a conjugate of a monoclonal antibody (mAb) and a photoactivatable silica phthalocyanine dye (IRDye700DX: IR700). Unlike conventional photodynamic therapy (PDT), NIR-PIT selectively destroys targeted tumor cells while preserving the surrounding normal tissue and providing superior tissue penetration. Recently, NIR-PIT has been approved for the treatment of unresectable recurrent head and neck cancers in Japan. It induces highly selective cancer cell death; therefore, it is expected to be a new curative treatment option for various cancers, including brain tumors. In this review, we compare the principles of NIR-PIT and PDT and discuss the potential applications of NIR-PIT for brain tumors. We selected targetable proteins across various types of brain tumors and devised a strategy to effectively pass the mAb-IR700 conjugate through the blood-brain barrier (BBB), which is a significant challenge for NIR-PIT in treating brain tumors. Innovative approaches for delivering the mAb-IR700 conjugate across the BBB include exosomes, nanoparticle-based systems, and cell-penetrating peptides. Small-molecule compounds, such as affibodies, are anticipated to rapidly accumulate in tumors within intracranial models, and our preliminary experiments demonstrated rapid uptake. NIR-PIT also induces immunogenic cell death and activates the anti-tumor immune response. Overall, NIR-PIT is a promising approach for treating brain tumors. It has the potential to overcome the limitations of conventional therapies and offers new hope to patients with brain tumors.

Keywords: IR700; brain metastasis; brain tumors; central nervous system; glioma; intraoperative treatment; laser; meningioma; near-infrared photoimmunotherapy; photodynamic therapy.

Figure 1

Mechanism of NIR-PIT: NIR-PIT utilizes IRDye700DX–antibody conjugates. When these conjugates bind to cancer cell receptors and are activated by 690 nm near-infrared light, IR700 undergoes photochemical reactions that convert it from hydrophilic to hydrophobic. This transformation leads to molecular aggregation, which disrupts cell membrane integrity and induces cell death. Solid black arrows indicate IR700Dye in each conjugate, while dotted black arrows indicate H₂O entering the cancer cells.

Figure 2

(a) The fluorescence intensity of the head increased dramatically immediately after the injection of the EGFR Affibody–IR700Dye conjugate. (b) Brain collection and fluorescence imaging were performed 1 h after i.v. injection of the EGFR Affibody–IR700 conjugate. (c) Fluorescent images of IR700 and hematoxylin/eosin staining after the brain was fixed overnight. Fluorescence accumulation is observed at the tumor site. The yellow arrows show the progression of the experimental timeline from left to right.