Protein-coated corrole nanoparticles for the treatment of prostate cancer cells

Abstract

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.

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

“…The death cases in 2018 from 359,000 is projected to increase up to 740,000 cases in 2040, with a rise of new cases from 1,276,000 in 2018 to 2.3 million in 2040, because of increased numbers of the aging population (Culp et al, 2020). Depending on the levels of prostate-specific antigen and clinical stage of the patients, the treatment of patients with prostate cancer has opted for active surveillance, radiotherapy, or prostatectomy (Soll et al, 2020). Treatment option of prostate cancer includes androgen deprivation therapy as the mainstay management, however, the condition might progress to castration-resistant prostate cancer.…”

Corroles at work: a small macrocycle for great applications

“…87). [235][236][237][238][239][240][241] Corrole conjugates have been the subject of a recent review from Sessler and coworker. 242 Main group corroles and their photophysical properties have been recently reviewed by Gross and Churchill.…”

“…Fig.87Gallium A 3 -and trans-A 2 B-corrole complexes tested as potential photosensitizers in PDT [235][236][237][238][239][240][241]. …”

Gallium (III) Complexes in Cancer Chemotherapy

“…[91] Recently, a lipophilic Ga(III) corrole delivered in as human serum albumin (HSA)-coated NPs (Ga/ HSA NPs), displayed antineoplastic activity towards human prostate cancer DU-145 cells. [82] These NPs were taken up via endocytosis and induced plasma membrane destabilization, impairment of calcium homeostasis, lysosomal stress and rupture, generation of reactive oxygen species (ROS), and consequently necrosis (Figure 5). These studies demonstrated the distinctive action of Ga(III) corroles and also provided abundant strategies to design and deliver Ga(III) compounds with enhancing drug concentration.…”