Format

Send to

Choose Destination
Biomaterials. 2014 May;35(16):4688-98. doi: 10.1016/j.biomaterials.2014.02.030. Epub 2014 Mar 6.

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

Author information

1
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.
2
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
3
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.

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.

KEYWORDS:

LCP; Lymph node; Lymphotropism; Metastasis; Nanoparticle; SPECT

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center