Biocompatible Gadolinium Oxide Nanoparticles Incorporated Doxorubicin Enables Magnetic Resonance and Photoacoustic Dual Imaging for Cancer Theranostics.

The engineering of theranostic nanoparticles, which integrate diagnostics and therapy in a single administration, enables targeted drug delivery and disease visualization. In cancer theranostics, gadolinium-based nanoparticles are valuable tools for noninvasive magnetic resonance imaging (MRI) and provide high-resolution images of the tumor. When MRI is combined with other imaging modalities, complementary therapeutic information is obtained for more accurate identification of tumor characteristics and precise guidance of anticancer drug delivery. Among the many possible modalities combined with MRI, photoacoustic imaging (PAI) is a candidate that enables sensitive in vivo detection of tumors. We have already succeeded in synthesizing biocompatible gelatin-coated gadolinium oxide nanoparticles with a controlled size by adjusting the timing of gelatin addition, which were a highly efficient contrast agent for MR and PA dual imaging. Herein, we conjugated a clinically used anticancer drug (doxorubicin, DOX) to size-defined and biocompatible gadolinium oxide nanoparticles which are novel theranostic probes. Succinylated gelatin enabled the electrostatic conjugation of DOX with gadolinium oxide nanoparticles, and the release of DOX was controlled through the enzymatic degradation of gelatin by matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), which are highly expressed in cancer cells. The released DOX efficiently inhibited the growth of HeLa cells in vitro and the growth of the inoculated tumor tissues in vivo. The dual-modality MRI and PAI capabilities provide anatomical information that assists in the localization and targeting of theranostic probes.