Protein-coated corrole nanoparticles for the treatment of prostate cancer cells
| Autor: | Harry B. Gray, John Termini, Benny Zhitomirsky, Qiu-Cheng Chen, Matan Soll, Yehuda G. Assaraf, Zeev Gross, Punnajit Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research media_common.quotation_subject Immunology Drug development Apoptosis Endocytosis lcsh:RC254-282 Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine medicine Corrole lcsh:QH573-671 Internalization Cytotoxicity media_common Ion transport chemistry.chemical_classification Reactive oxygen species Chemistry lcsh:Cytology Cell Biology Human serum albumin lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Calcium channels 030104 developmental biology Mechanism of action 030220 oncology & carcinogenesis Drug delivery Biophysics medicine.symptom medicine.drug |
| Zdroj: | Cell Death Discovery Cell Death Discovery, Vol 6, Iss 1, Pp 1-17 (2020) |
| ISSN: | 2058-7716 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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