Development of Photoactive Sweet-C ₆₀ for Pancreatic Cancer Stellate Cell Therapy

Abstract

Aim: Glycoconjugated C 60 derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells. Materials & methods: Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C 60 derivative (termed 'Sweet-C 60 '). Results: Synthesized fullerene derivative predominantly accumulates in the nucleus of pancreatic stellate cells; is inherently nontoxic up to concentrations of 1 mg/ml; and is photoactive when illuminated with blue and green light, allowing its use as a photodynamic therapy agent. Conclusion: Obtained glycoconjugated nanoplatform is a promising nanotherapeutic for pancreatic cancer.

THE A water-soluble [60]fullerene-derivative stimulates chlorophyll accumulation and has no toxic effect on Chlamydomonas reinhardtii

“…Highly water-soluble glycine derivative of [60]fullerene was synthesized using previously developed methodology (Serda et al, 2018a;Serda et al, 2018b).…”

A [60]fullerene nanoconjugate with gemcitabine: synthesis, biophysical properties and biological evaluation for treating pancreatic cancer

“…Diserinol malonate and its peracetylated version were synthesized on a large scale using a modified protocol (Serda et al 2018). Briefly, 2-amino-1,3-propanediol (100 g, 1076 mmol) and dimethyl malonate (57.4 mL, 500 mmol) were dissolved in dry isopropanol, heated with vigorous stirring at 50 °C for 30 min and then stirred at room temperature, under a nitrogen atmosphere for 14 days.…”

“…Spin trapping was performed in 80% DMSO, which made any measurements in the presence of BSA impossible as it would have destroyed the protein structure. Although the photoreactivity of our novel fullerene nanomaterial is not very high, its localization within cancer cells could make it more phototoxic if it is localized, for example, in the nucleus (Serda et al 2018).…”

“…Appropriately derivatized [60]fullerene buckyballs become amphiphilic in nature with the ability to cross most biological barriers, including the blood-brain barrier and nuclear membrane (Raoof et al 2012). Furthermore, fullerene nanomaterials are non-toxic even at high concentrations of up to 1 mg/mL (Serda et al 2018). The anti-cancer activity of fullerenes has mainly been described for in vivo models, where it has been explained by its ability to inhibit tumor angiogenesis (metalloproteinases inhibitors) and its strong antioxidant properties (Chen et al 2005;Sun et al 2016).…”

Evaluation of the Biodistribution of Serinolamide-Derivatized C60 Fullerene

“…Inherently, C 60 has also shown strong antioxidant behavior through its ability to quench free radicals [17,18] and has been observed to nearly double the lifespan of rodents, presumably because of this radical-scavenging property [19,20]. Conversely, certain C 60 derivatives can generate reactive oxygen species under light irradiation, allowing these derivatives to be used for photodynamic therapy (PDT) against cancer [21,22]. Furthermore, C 60 can be chemically decorated with molecular targeting agents [23,24], imaging agents [25][26][27], and anticancer drugs [24,[28][29][30][31] to be used as a therapeutic delivery vector, a diagnostic agent, or a combination of the two (known as a theranostic agent).…”