Lipid-calcium phosphate nanoparticles for delivery to the lymphatic system and SPECT/CT imaging of lymph node metastases

A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter 25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of In-111 into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted In-111-LCP preferentially accumulated in the lymph nodes at similar to 70% ID/g in both C57BL/6 and nude mice when the improved surface coating method was used. Both the liver and spleen accumulated only similar to 25% ID/g. Larger LCP (diameter similar to 67 nm) was less lymphotropic. These results indicate that 25 nm LCP was able to penetrate into tissues, enter the lymphatic system, and accumulate in the lymph nodes via lymphatic drainage due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The capability of intravenously injected In-111-LCP to visualize an enlarged, tumor-loaded sentinel lymph node was demonstrated using a 4T1 breast cancer lymph node metastasis model. Systemic gene delivery to the lymph nodes after IV injection was demonstrated by the expression of red fluorescent protein cDNA. The potential of using LCP for lymphatic drug delivery is discussed. (C) Published by Elsevier Ltd.