Abstract:
Photodynamic therapy (PDT) is a noninvasive approach to cancer treatment, wherein cell death is initiated by singlet oxygen (1O2) production via energy transfer from excited photosensitizers to ground-state O2. Effective clinical photosensitizers necessitate water solubility for in vivo administration. Hydrophobic dyes, such as phthalocyanines, cannot be used directly as photosensitizers. Herein, we synthesized a myoglobin-(human serum albumin) fusion protein reconstituted with zinc-phthalocyanine (ZnPc), termed ZnPcMb-HSA. The photophysical properties of ZnPcMb-HSA closely resemble those of ZnPc-substituted Mb. Notably, ZnPc dissociates from ZnPcMb-HSA and selectively accumulates within cancer cells, while the protein components remain extracellular. Treatment of four distinct cell lines with ZnPcMb-HSA, followed by red-light irradiation, effectively induced apoptosis. The half-maximal inhibitory concentrations (IC50) against these cancer cell lines ranged between 0.1-0.5 μM. Reconstituted Mb-HSA emerges as a promising carrier for transporting various water-insoluble porphyrinoid photosensitizer to target cancer cells in PDT applications.
摘要:
光动力疗法(PDT)是一种非侵入性的癌症治疗方法,其中通过从激发的光敏剂到基态O2的能量转移产生单线态氧(1O2)引发细胞死亡。有效的临床光敏剂需要水溶性以用于体内给药。疏水染料,如酞菁,不能直接用作光敏剂。在这里,我们合成了一个用锌酞菁(ZnPc)重建的肌球蛋白(人血清白蛋白)融合蛋白,称为ZnPcMb-HSA。ZnPcMb-HSA的光物理性质与ZnPc取代的Mb非常相似。值得注意的是,ZnPc从ZnPcMb-HSA分离并选择性地在癌细胞内积累,而蛋白质成分保持在细胞外。用ZnPcMb-HSA处理四种不同的细胞系,接着是红光照射,有效诱导细胞凋亡。针对这些癌细胞系的半最大抑制浓度(IC50)在0.1-0.5μM之间。重构的Mb-HSA作为在PDT应用中运输各种水不溶性卟啉类光敏剂以靶向癌细胞的有前途的载体出现。