Head and neck squamous cell carcinoma (HNSCC) still represents the world’s sixth most common tumor entity, with increasing incidence. The reachability of light makes HNSCC suitable for light-based therapies such as Photochemical Internalization (PCI). The drug Bleomycin is cytotoxic and used as an anti-tumor medication. Since Bleomycin is endocytosed as a relatively large molecule, part of it is degraded in lysosomes before reaching its intracellular target. The goal of our study was to improve the intracellular availability of Bleomycin with PCI. We investigate the intracellular delivery of Bleomycin after PCI with the photosensitizer Fimaporfin. A systematic variation of Bleomycin and Fimaporfin concentrations and light irradiation led to the pronounced cell death of HNSCC cells. After optimization, the same level of tumor cell death of 75% was reached with a 20-fold lower Bleomycin concentration. This would allow treatment of HNSCC with high local tumor cell death and reduce the side effects of Bleomycin, e.g., lung fibrosis, at the same time. This demonstrates the increased efficacy of the anti-tumor medication Bleomycin in combination with PCI.

In cholesteatoma surgery, precise tissue resection is important, as the diseased tissue needs to be completely removed while preserving the ossicular chain to prevent recurrence and hearing loss. The ability to precisely ablate tissue using a pulsed [Formula: see text] diode laser operating in single-trigger mode was investigated. Single laser pulses with a duration of [Formula: see text] were applied with a power ranging from [Formula: see text] via a multimode optical fiber. Fiber distance to tissue was varied from [Formula: see text], and irradiation angles from [Formula: see text]. Porcine ear cartilage with [Formula: see text] remaining perichondrium on top served to represent the human ossicle structure with cholesteatoma. Further ablation experiments were performed on human cholesteatoma and ossicle samples. Ablation craters were measured by optical coherence tomography (OCT), and tissue damage assessed with haematoxylin and eosin (H&E)-stained sections. The ablation depth reached up to [Formula: see text] when operating at [Formula: see text] power output without causing damage to the underlying cartilage. Laser pulses with [Formula: see text] successfully ablated cholesteatoma, but did not damage the ossicles. The results show that a [Formula: see text] diode laser pulses can be used to effectively remove cholesteatoma, potentially preserving ossicles and hearing ability.