This study reports the design of a novel theragnostic nanomedicine which combines (i) the ability to target a
prodrug of
gemcitabine to an experimental solid
tumor under the influence of a magnetic field with (ii) the imaging of the targeted tumoral nodule. This concept is based on the inclusion of
magnetite nanocrystals into nanoparticles (NPs) constructed by self-assembling molecules of the squalenoyl
gemcitabine (SQgem) bioconjugate. The nanocomposites are characterized by an unusually high drug loading, a significant magnetic susceptibility, and a low burst release. When injected to the L1210 subcutaneous mice
tumor model, these
magnetite/SQgem NPs were magnetically guided, and they displayed considerably greater anticancer activity than the other anticancer treatments (
magnetite/SQgem NPs nonmagnetically guided, SQgem NPs, or
gemcitabine free in
solution). The histology and immunohistochemistry investigation of the
tumor biopsies clearly evidenced the therapeutic superiority of the magnetically guided nanocomposites, while
Prussian blue staining confirmed their accumulation at the
tumor periphery. The superior therapeutic activity and enhanced
tumor accumulation has been successfully visualized using T(2)-weighted imaging in magnetic resonance imaging (MRI). This concept was further enlarged by (i) the design of
squalene-based NPs containing the T(1)
Gd(3+)
contrast agent instead of
magnetite and (ii) the application to other anticancer squalenoyls, such as,
cisplatin,
doxorubicin, and
paclitaxel. Thus, by combining different anticancer medicines as well as contrast imaging agents in NPs, we open the door toward generic conceptual framework for
cancer treatment and diagnosis. This new theragnostic nanotechnology platform is expected to have important applications in
cancer therapy.