High-Load Nanoparticles with Chemotherapeutic SN-38/FdUMP Drug Cocktail

Abstract

[Gd(OH)]2+[(SN-38)0.5(FdUMP)0.5]2 inorganic-organic hybrid nanoparticles (IOH-NPs) with a chemotherapeutic cocktail of ethyl-10-hydroxycamptothecin (SN-38, active form of irinotecan) and 5-fluoro-2'-deoxyuridine-5'-phosphate (FdUMP, active form of 5’-fluoruracil), 40 nm in diameter, are prepared in water. The IOH-NPs contain a total drug load of 63 wt-% with 33 wt-% of SN-38 and 30 wt-% of FdUMP. Cell-based assays show efficient cellular uptake and promising anti-tumour activity on two pancreatic cancer cell lines of murine origin (KPC, Panc02). Beside the high-load drug cocktail especially the option to use SN-38, which – although 100- to 1,000-times more potent than irinotecan – is usually unsuitable for systemic administration due to poor solubility, low stability, and high toxicity upon non-selective delivery. The [Gd(OH)]2+[(SN-38)0.5(FdUMP)0.5]2 IOH-NPs are a new concept to deliver a drug cocktail with SN-38 and FdUMP directly to the tumour, shielded in a nanoparticle, to reduce side effects.