Development of novel therapeutic strategies to eradicate malignant tumors is of paramount importance in cancer research. In a recent study, we have introduced a facile protocol for the preparation of corrole-protein nanoparticles (NPs). These NPs consist of a corrole-core coated with protein. We now report that a novel lipophilic corrole, (2)Ga, delivered as human serum albumin (HSA)-coated NPs, displayed antineoplastic activity towards human prostate cancer DU-145 cells. Cryo-TEM analysis of these NPs revealed an average diameter of 50.2 ± 8.1 nm with a spherical architecture exhibiting low polydispersity. In vitro cellular uptake of (2)Ga/albumin NPs was attributable to rapid internalization of the corrole through ligand binding-dependent extracellular release and intercalation of the corrole cargo into the lipid bilayer of the plasma membrane. This finding is in contrast with a previously reported study on corrole-protein NPs that displayed cellular uptake via endocytosis. Investigation of the non-light-induced mechanism of action of (2)Ga suggested the induction of necrosis through plasma membrane destabilization, impairment of calcium homeostasis, lysosomal stress and rupture, as well as formation of reactive oxygen species (ROS). (2)Ga also exhibited potent light-induced cytotoxicity through ROS generation. These findings demonstrate a rapid cellular uptake of (2)Ga/protein NPs along with targeted induction of tumor cell necrosis.

开发新的治疗策略来根除恶性肿瘤对于癌症研究至关重要。在最近的一项研究中，我们引入了一种用于制备咔咯蛋白纳米颗粒（NP）的简便方案。这些纳米颗粒由涂有蛋白质的咔咯核组成。我们现在报道了一种新型亲脂性咔咯（2）Ga，以人血清白蛋白（HSA）包被的纳米颗粒形式递送，对人前列腺癌 DU-145 细胞表现出抗肿瘤活性。这些 NP 的冷冻 TEM 分析显示平均直径为 50.2 ± 8.1 nm，具有低多分散性的球形结构。( 2 )Ga/白蛋白纳米粒子的体外细胞摄取归因于通过配体结合依赖性胞外释放和咔咯货物嵌入质膜的脂质双层而快速内化咔咯。这一发现与之前报道的咔咯蛋白纳米粒子的研究形成鲜明对比，该研究显示细胞通过内吞作用进行摄取。对 ( 2 )Ga非光诱导作用机制的研究表明，通过质膜不稳定、钙稳态受损、溶酶体应激和破裂以及活性氧 (ROS) 的形成诱导坏死。( 2 )Ga 还通过 ROS 的产生表现出强效的光诱导细胞毒性。这些发现表明细胞对 ( 2 )Ga/蛋白质纳米颗粒的快速摄取以及肿瘤细胞坏死的靶向诱导。