Manganese-Doped N-Hydroxyphthalimide-Derived Carbon Dots-Theranostics Applications in Experimental Breast Cancer Models.

BACKGROUND: Theranostics, a novel concept in medicine, is based on the use of an agent for simultaneous diagnosis and treatment. Nanomaterials provide promising novel approaches to theranostics. Carbon Dots have been shown to exhibit anti-tumoral properties in various cancer models. The aim of the present study is to develop gadolinium, Fe3+, and Mn2+-doped N-hydroxyphthalimide-derived Carbon Dots. The resulted doped Carbon Dots should preserve the anti-tumoral properties while gaining magnetic resonance imaging properties. METHODS: Normal and cancer cell lines have been treated with doped Carbon Dots, and the cell viability has been measured. The doped Carbon Dots that exhibited the most prominent anti-tumoral effect accompanied by the lowest toxicity have been further in vivo tested. Magnetic resonance imaging evaluates both in vitro and in vivo the possibility of using doped Carbon Dots as a contrast agent. RESULTS: According to the results obtained from both the in vitro and in vivo experimental models used in our study, Mn2+-doped Carbon Dots (Mn-CDs-NHF) exhibit anti-tumoral properties, do not significantly impair the cell viability of normal cells, and reduce lung metastasis and the volume of mammary primary tumors while allowing magnetic resonance imaging. CONCLUSIONS: Our findings prove that Mn-CDs-NHF can be used as theranostics agents in pre-clinical models.

ABL1 tyrosine kinase domain mutations in chronic myeloid leukemia treatment resistance.

The development of mutations in the BCR-ABL1 fusion gene transcript causes resistance to tyrosine kinase inhibitors (TKIs) based therapy in chronic myeloid leukemia (CML). Thereby, screening for BCR-ABL1 mutations is advised especially in patients undergoing poor response to treatment. In the current study the authors investigated 43 patients with CML that failed or had suboptimal response to TKIs treatment. Blood samples were collected from patients that were treated with TKIs. The analysis of genetic mutations was performed using a semi-nested PCR assay, followed by Sanger sequencing. The analysis revealed 15 mutations (32.55%): 14 point mutations and an exon 7 deletion. In roughly 30% of cases, mutations in the BCR-ABL1 fusion gene are common causes for treatment resistance.