Enhancing Anti-Tumoral Potential of CD-NHF by Modulating PI3K/Akt Axis in U87 Ex Vivo Glioma Model

Abstract

Background: In the latest years, there has been an increased interest in nanomaterials that may provide promising novel approaches to disease diagnostics and therapeutics. Our previous results demonstrated that Carbon-dots prepared from N-hydroxyphthalimide (CD-NHF) exhibited anti-tumoral activity on several cancer cell lines such as MDA-MB-231, A375, A549, and RPMI8226, while U87 glioma tumor cells were unaffected. Gliomas represent one of the most common types of human primary brain tumors and are responsible for the majority of deaths. In the present in vitro study, we expand our previous investigation on CD-NHF in the U87 cell line by adding different drug combinations. Methods: Cell viability, migration, invasion, and immunofluorescent staining of key molecular pathways have been assessed after various treatments with CD-NHF and/or K252A and AKTVIII inhibitors in the U87 cell line. Results: Association of an inhibitor strongly potentiates the anti-tumoral properties of CD-NHF identified by significant impairment of migration, invasion, and expression levels of phosphorylated Akt, p70S6Kinase, or by decreasing expression levels of Bcl-2, IL-6, STAT3, and Slug. Conclusions: Using simultaneously reduced doses of both CD-NHF and an inhibitor in order to reduce side effects, the viability and invasiveness of U87 glioma cells were significantly impaired.

Tumor diagnosis using carbon-based quantum dots: Detection based on the hallmarks of cancer

“…The in vitro investigations showed that the level of IL-6 mRNA in cancer cells treated with Mn-doped CDs-NHF was significantly lower than that in the control cells (which were treated with Gadovist, a gadolinium-based contrast agent). Luta et al [ 381 ] found a significant impairment in the IL-6 level in all of their groups treated with CDs-NHF thus confirming the antitumoral properties of these CDs.…”

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

“…Since the widely used contrast agent, gadolinium, presents various side effects, we aimed to develop theranostic agents by doping CDs-NHF with ions that present lower toxicity. Previously, we have demonstrated the anti-tumoral properties of non-doped CDs-NHF in various models [ 15 , 16 , 42 ]. In our new experimental investigations, we decide to combine the anti-tumoral properties of CDs-NHF with MRI imaging capabilities of Gd 3+ , Fe 3+ , or Mn 2+ .…”

“…Our previous work demonstrated in vitro and in vivo the anti-tumoral properties of N-Hydroxyphthalimide-derived Carbon Dots (CDs-NHF) in a breast cancer model [ 15 ]. In another paper, we have shown that although CDs-NHF alone do not impair U87 glioblastoma cell line viability, combining lower doses of key pathways inhibitors with lower CDs-NHF doses significantly reduced cell viability [ 16 ].…”