title: Lipid-calcium phosphate nanoparticles for delivery to the lymphatic system and SPECT/CT imaging of lymph node metastases.
abstract: 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 (111)In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene glycol grafted (111)In-LCP preferentially accumulated in the lymph nodes at ∼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 ∼25% ID/g. Larger LCP (diameter ∼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 (111)In-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.
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Tseng
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Guley
authors.affiliation: Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA. Electronic address: leafh@email.unc.edu.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry; D005260:Female; D007205:Indium Radioisotopes; D008055:Lipids / Q000737:chemistry; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000000981:diagnostic imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D002130:Calcium Phosphates; D007205:Indium Radioisotopes; D008055:Lipids; C020243:calcium phosphate
keywords: LCP; Lymph node; Lymphotropism; Metastasis; Nanoparticle; SPECT