High-load nanoparticles with a chemotherapeutic SN-38/FdUMP drug cocktail

[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 size, 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 1000-times more potent than irinotecan – is usually unsuitable for sys-
temic 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.