Wioletta Kośnik

Biodistribution of Polyaldehydedextran Nanoparticle-Encapsulated Epirubicin in Ovarian Tumor-Bearing Mice via Optical Imaging

This study investigates the biodistribution of polysaccharide-based nanoparticles loaded with epirubicin (POLEPI) compared to epirubicin hydrochloride (EPI) in naïve female nude mice following a single intravenous dose. The inherent fluorescence of epirubicin was tracked using Newton 7 animal imager and Varioskan. Initial whole-animal optical imaging failed to reliably detect epirubicin distribution, necessitating ex vivo imaging of key tissues harvested at intervals between 10 min and 48 h post-injection. Optimal imaging conditions were established using a 5 s exposure time with excitation (Ex)/emission (Em) at 480 nm/550 nm. The biodistribution of POLEPI was further evaluated in both naïve mice and immunocompromised mice bearing patient-derived ovarian tumors. Unlike epirubicin, POLEPI exhibited notable tissue distribution within 3 h post-injection. By 48 h, fluorescence signals were undetectable in both models, although non-tumored animals exhibited persistent signals. In both models, the liver was the primary organ for POLEPI accumulation, with lower levels in tumored mice. Interestingly, brain fluorescence was higher in POLEPI-treated mice compared to those receiving epirubicin. Neither POLEPI nor epirubicin accumulated in the spleen or bone marrow. In tumors, POLEPI fluorescence peaked at 24 h, with levels 2.1 times higher than in the epirubicin-treated group over a 48 h period. Furthermore, POLEPI uptake in tumors exceeded that in healthy ovaries, with the most significant tumor-to-healthy-ovary ratio observed between 6 and 24 h post-injection. These findings demonstrate that POLEPI, a novel polyaldehydedextran nanoparticle formulation, exhibits enhanced accumulation and retention in tumor tissue compared to epirubicin, with preferential distribution to the orthotopic tumor-bearing ovary over healthy ovarian tissue. The inherent fluorescence of epirubicin provided a rapid and cost-effective means of estimating biodistribution, although the limitations of this method—particularly, the inability to differentiate between the parent drug and its metabolites—were acknowledged.

Nanoparticle-Encapsulated Epirubicin Efficacy in the Inhibition of Growth of Orthotopic Ovarian Patient-Derived Xenograft in Immunocompromised Mice

Epirubicin hydrochloride (EPI) is an anticancer drug widely used in the treatment of many solid tumors, including ovarian cancer. Because of its anatomical location, ovarian cancer shows symptoms when it is already in an advanced stage and is thus more difficult to treat. Epirubicin hydrochloride kills cancer cells effectively, but its dose escalation is limited by its severe toxicity. By encapsulating epirubicin in dextran-based nanoparticles (POLEPI), we expected to deliver higher and thus clinically more effective doses directly to tumors, where epirubicin would be released and retained longer in the tumor. The antitumor activity of POLEPI compared to EPI was first tested ex vivo in a series of ovarian cancer patient-derived tumor xenografts (PDX). The most promising PDX was then implanted orthotopically into immunocompromised mice, and tumor growth was monitored via magnetic resonance imaging (MRI). Although we succeeded in suppressing the growth of ovarian cancer derived from a patient, in a mouse model by 70% compared to 40% via EPI in 5 days after only one injection, we could not eliminate serious side effects, and the study was terminated prematurely for humane reasons.