| Autor: |
Paudyal S; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States., Vallejo FA; Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, United States.; University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, United States., Cilingir EK; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States., Zhou Y; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States., Mintz KJ; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States., Pressman Y; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, United States., Gu J; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States., Vanni S; Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, United States.; HCA Florida University Hospital, 3476 S University Dr., Davie, Florida 33328, United States.; Department of Medicine, Dr. Kiran C. Patel College of Allopathic Medicine, Davie, Florida 33328, United States., Graham RM; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States.; University of Miami Brain Tumor Initiative, Department of Neurosurgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Miami, Florida 33136, United States.; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida 33136, United States., Leblanc RM; Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146, United States. |
| Abstrakt: |
Neuroblastoma (NB) is a pediatric malignancy affecting the peripheral nervous system. Despite recent advancements in treatment, many children affected with NB continue to submit to this illness, and new therapeutic strategies are desperately needed. In recent years, studies of carbon dots (CDs) as nanocarriers have mostly focused on the delivery of anticancer agents because of their biocompatibility, good aqueous dissolution, and photostability. Their fluorescence properties, surface functionalities, and surface charges differ on the basis of the type of precursors used and the synthetic approach implemented. At present, most CDs are used as nanocarriers by directly linking them either covalently or electrostatically to drug molecules. Though most modern CDs are synthesized from large carbon macromolecules and conjugated to anticancerous drugs, constructing CDs from the anticancerous drugs and precursors themselves to increase antitumoral activity requires further investigation. Herein, CDs were synthesized using difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor commonly used in high-risk neuroblastoma treatment regiments. In this study, NB cell lines, SMS-KCNR and SK-N-AS, were treated with DFMO, the newly synthesized DFMO CDs, and conventional DFMO conjugated to black carbon dots. Bioimaging was done to determine the cellular localization of a fluorescent drug over time. The mobility of DNA mixed with DFMO CDs was evaluated by gel electrophoresis. DFMO CDs were effectively synthesized from DFMO precursor and characterized using spectroscopic methods. The DFMO CDs effectively reduced cell viability with increasing dose. The effects were dramatic in the N-MYC-amplified line SMS-KCNR at 500 μM, which is comparable to high doses of conventional DFMO at a 60-fold lower concentration . In vitro bioimaging as well as DNA electrophoresis showed that synthesized DFMO CDs were able to enter the nucleus of neuroblastoma cells and neuronal cells and interact with DNA. Our new DFMO CDs exhibit a robust advantage over conventional DFMO because they induce comparable reductions in viability at a dramatically lower concentration. |
