(241d) Gadolinium-Loaded Chitosan Nanoparticles for Cancer Neutron-Capture Therapy: Pharmaceutical Characteristics and in Vitro Antitumor Effect

The aim of the present study is to modify the original gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs) to obtain a higher effect in the neutron-capture therapy (NCT). Pharmaceutical characteristics, cell-association in vitro and antitumor effect in vitro were evaluated using various Gd-nanoCPs. Preparation of Gd-nanoCPs was carried out based on the w/o emulsion-droplet coalescence technique with a slight modification. Chitosan with different molecular weight (Mw) (950, 50, 10 kDa) was applied at various concentrations (0.5, 1.5, 2.5%). B16F10 mouse melanoma cells were employed to evaluate the cell-association properties of Gd-nanoCPs and the antitumor effect with thermal neutron irradiation. Antitumor effects were evaluated by colony assay method after thermal neutron irradiation. In the formulation study on Gd-nanoCPs, as the Mw of chitosan decreased, the mean particle diameter decreased to 155 nm with 10 kDa chitosan at the smallest. Then, decrease in the chitosan concentration in the chitosan solution contributed to a decrease in mean particle diameter and a increase in gadolinium content. The Gd content in the Gd-nanoCPs prepared with 0.5% chitosan reached 22% at the maximum. The amount of Gd associated with cells was also dependent on the Mw of chitosan: when the cells were incubated with Gd-nanoCPs formulated at 0.5% of 10 kDa and 50 kDa chitosan, the Gd cell-assiciated was 2.2- and 1.9-fold higher than that in the case of 950 kDa chitosan, respectively. In the subsequent Gd-NCT study in vitro, the most highly Gd-containing (22%) and finest (155 nm) Gd-nanoCPs prepared at 0.5% of 10 kDa exhibited the strongest tumor growth suppression. It is expected that use of Gd-nanoCP prepared here will lead to improved treatment of cancer by NCT.