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

• Published in: Journal of controlled release Vol. 217; pp. 170 - 182
• Main Authors: Satterlee, Andrew B., Yuan, Hong, Huang, Leaf
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.11.2015
• Subjects: Animals; Apoptosis - drug effects; Calcium Phosphates - administration & dosage; Calcium Phosphates - pharmacokinetics; Calcium Phosphates - therapeutic use; Cancer; Cell Line, Tumor; DNA Damage; Female; High specific drug loading; Humans; Lutetium - administration & dosage; Lutetium - pharmacokinetics; Lutetium - therapeutic use; Mice; Mice, Nude; Nanoparticle; Nanoparticles - administration & dosage; Nanoparticles - therapeutic use; Neoplasms - diagnosis; Neoplasms - drug therapy; Neoplasms - metabolism; NIH 3T3 Cells; Radioisotopes - administration & dosage; Radioisotopes - pharmacokinetics; Radioisotopes - therapeutic use; Theranostic; Theranostic Nanomedicine; Tomography, Emission-Computed, Single-Photon; Tumor Microenvironment - drug effects; AA; EE; High specific drug loading; Nanoparticle; DSPE-PEG2000; Ksp; Lu; SPECT; EDS; Theranostic; LCP; DOPA; TEM; DOPC; Cancer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2015.08.048

We have developed a theranostic nanoparticle delivering the model radionuclide 177Lu based on the versatile lipid-calcium-phosphate (LCP) nanoparticle delivery platform. Characterization of 177Lu-LCP has shown that radionuclide loading can be increased by several orders of magnitude without affecting the encapsulation efficiency or the morphology of 177Lu-LCP, allowing consistency during fabrication and overcoming scale-up barriers typical of nanotherapeutics. The choice of 177Lu as a model radionuclide has allowed in vivo anticancer therapy in addition to radiographic imaging via the dual decay modes of 177Lu. Tumor accumulation of 177Lu-LCP was measured using both SPECT and Cerenkov imaging modalities in live mice, and treatment with just one dose of 177Lu-LCP showed significant in vivo tumor inhibition in two subcutaneous xenograft tumor models. Microenvironment and cytotoxicity studies suggest that 177Lu-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. [Display omitted]