Gadolinium-Loaded Chitosan Nanoparticles for Cancer Neutron-Capture Therapy: Pharmaceutical Characteristics and In Vitro Antitumor Effect

摘要

Preparation of Gd-nanoCPs was carried out based on the w/o emulsion-droplet coalescence technique. 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. 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 an 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. 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 chitosan exhibited the strongest tumor cell growth suppression. It is expected that use of Gd-nanoCP prepared here will lead to improved treatment of cancer by NCT.