光化学内化(PCI)与Fimaporfin:头颈部肿瘤增强型博莱霉素治疗
Photochemical Internalization with Fimaporfin: Enhanced Bleomycin Treatment for Head and Neck Cancer.
发表日期:2023 Jul 28
作者:
Paula Enzian, Ramtin Rahmanzadeh
来源:
Cell Death & Disease
摘要:
头颈鳞状细胞癌(HNSCC)仍然是世界上第六常见的肿瘤,且发病率逐渐增加。光的可达性使HNSCC适用于基于光的治疗,如光化学内化(PCI)。Bleomycin药物具有细胞毒性,被用作抗肿瘤药物。由于Bleomycin作为相对较大的分子被内吞,它的一部分在溶酶体中降解后才能到达细胞内靶点。我们的研究目标是通过PCI改善Bleomycin在细胞内的可用性。我们调查了Fimaporfin光敏剂与Bleomycin在PCI后的细胞内传递。对Bleomycin和Fimaporfin浓度以及光照进行系统变化,导致HNSCC细胞的明显细胞死亡。经过优化后,仅使用20倍较低的Bleomycin浓度就能达到相同水平的肿瘤细胞死亡率,达到75%。这将允许高局部肿瘤细胞死亡的HNSCC治疗,同时减少Bleomycin的副作用,如肺纤维化。这表明Bleomycin与PCI联合使用的抗肿瘤药物疗效增加。
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.