A radio-theranostic nanoparticle with high specific drug loading for cancer therapy and imaging

We have developed a theranostic nanoparticle delivering the model radionuclide Lu-177 based on the versatile lipid-calcium-phosphate (LCP) nanoparticle delivery platform. Characterization of Lu-177-LCP has shown that radionuclide loading can be increased by several orders of magnitude without affecting the encapsulation efficiency or the morphology of Lu-177-LCP, allowing consistency during fabrication and overcoming scale-up barriers typical of nanotherapeutics. The choice of Lu-177 as a model radionuclide has allowed in vivo anticancer therapy in addition to radiographic imaging via the dual decay modes of Lu-177. Tumor accumulation of Lu-177-LCP was measured using both SPECT and Cerenkov imaging modalities in live mice, and treatment with just one dose of Lu-177-LCP showed significant in vivo tumor inhibition in two subcutaneous xenograft tumor models. Microenvironment and cytotoxicity studies suggest that Lu-177-LCP inhibits tumor growth by causing apoptotic cell death via double-stranded DNA breaks while causing a remodeling of the tumor microenvironment to a more disordered and less malignant phenotype. (c) 2015 Elsevier B.V. All rights reserved.