Yamaguchi Haruka, Okada Masayasu, Otani Takuya, On Jotaro, Shibuma Satoshi, Takino Toru, Watanabe Jun, Tsukamoto Yoshihiro, Ogura Ryosuke, Oishi Makoto, Suzuki Takamasa, Ishikawa Akihiro, Sakata Hideyuki, Natsumeda Manabu
Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan.
Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Pharmaceuticals (Basel). 2025 May 19;18(5):751. doi: 10.3390/ph18050751.
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.
近红外光免疫疗法（NIR-PIT）是一种很有前景的癌症治疗方法，它利用近红外光激活单克隆抗体（mAb）与光活化硅酞菁染料（IRDye700DX：IR700）的偶联物。与传统光动力疗法（PDT）不同，NIR-PIT能选择性地破坏靶向肿瘤细胞，同时保留周围正常组织，并具有更强的组织穿透性。最近，NIR-PIT在日本已被批准用于治疗不可切除的复发性头颈癌。它能诱导高度选择性的癌细胞死亡；因此，有望成为包括脑肿瘤在内的各种癌症的一种新的治愈性治疗选择。在本综述中，我们比较了NIR-PIT和PDT的原理，并讨论了NIR-PIT在脑肿瘤治疗中的潜在应用。我们筛选了各种类型脑肿瘤中的可靶向蛋白，并设计了一种策略，以有效地使mAb-IR700偶联物通过血脑屏障（BBB），这是NIR-PIT治疗脑肿瘤面临的一项重大挑战。使mAb-IR700偶联物通过血脑屏障的创新方法包括外泌体、基于纳米颗粒的系统和细胞穿透肽。小分子化合物，如亲和体，预计能在颅内模型的肿瘤中快速积累，我们的初步实验也证明了其快速摄取。NIR-PIT还能诱导免疫原性细胞死亡并激活抗肿瘤免疫反应。总体而言，NIR-PIT是一种很有前景的脑肿瘤治疗方法。它有可能克服传统疗法的局限性，为脑肿瘤患者带来新的希望。
