DFMO Carbon Dots for Treatment of Neuroblastoma and Bioimaging

被引:7
作者
Paudyal, Suraj [1 ]
Vallejo, Frederic Anthony [2 ,3 ]
Cilingir, Emel Kirbas [1 ]
Zhou, Yiqun [1 ]
Mintz, Keenan J. [1 ]
Pressman, Yelena [4 ]
Gu, Jun [1 ]
Vanni, Steven [2 ,5 ,6 ,7 ]
Graham, Regina M. [1 ,3 ,8 ]
Leblanc, Roger M. [1 ]
机构
[1] Univ Miami, Dept Chem, Coral Gables, FL 33146 USA
[2] Univ Miami, Dept Neurosurg, Miller Sch Med, Miami, FL 33136 USA
[3] Univ Miami, Univ Miami Brain Tumor Initiat, Dept Neurosurg, Miller Sch Med, Miami, FL 33136 USA
[4] Univ Miami, Miami Project Cure Paralysis, Miller Sch Med, Miami, FL 33136 USA
[5] HCA Florida Univ Hosp, Davie, FL 33328 USA
[6] HCA Florida Univ Hosp, Davie, FL 33328 USA
[7] Dr Kiran C Patel Coll Allopath Med, Dept Med, Davie, FL 33328 USA
[8] Univ Miami Hlth Syst, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
基金
美国国家科学基金会;
关键词
carbon dots; DFMO; neuroblastoma; bioimaging; anticancer; nanoparticle; DIFLUOROMETHYLORNITHINE DFMO; THERANOSTIC AGENTS; NANOPARTICLES; CANCER; DELIVERY; TARGET; CYTOTOXICITY; INHIBITOR; TUMOR; MYCN;
D O I
10.1021/acsabm.2c00309
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 mu M, 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.
引用
收藏
页码:3300 / 3309
页数:10
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