LCP Nanoparticle for Tumor and Lymph Node Metastasis Imaging
Public DepositedAdd to collection
You do not have access to any existing collections. You may create a new collection.
Downloadable Content
Download PDFCitation
MLA
Tseng, Yu Cheng. Lcp Nanoparticle for Tumor and Lymph Node Metastasis Imaging. University of North Carolina at Chapel Hill, 2013. https://doi.org/10.17615/ym28-vr43APA
Tseng, Y. (2013). LCP Nanoparticle for Tumor and Lymph Node Metastasis Imaging. University of North Carolina at Chapel Hill. https://doi.org/10.17615/ym28-vr43Chicago
Tseng, Yu Cheng. 2013. Lcp Nanoparticle for Tumor and Lymph Node Metastasis Imaging. University of North Carolina at Chapel Hill. https://doi.org/10.17615/ym28-vr43- Last Modified
- March 22, 2019
- Creator
-
Tseng, Yu-Cheng
- Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
- Abstract
- A lipid/calcium/phosphate (LCP) nanoparticle formulation (particle diameter ~25 nm) has previously been developed to delivery siRNA with superior efficiency. In this work, 111In was formulated into LCP nanoparticles to form 111In-LCP for SPECT/CT imaging. With necessary modifications and improvements of the LCP core-washing and surface-coating methods, 111In-LCP grafted with polyethylene glycol exhibited reduced uptake by the mononuclear phagocytic system. SPECT/CT imaging supported performed biodistribution studies, showing clear tumor images with accumulation of 8% or higher injected dose per gram tissue (ID/g) in subcutaneous, human-H460, lung-cancer xenograft and mouse-4T1, breast cancer metastasis models. Both the liver and the spleen accumulated ~20% ID/g. Accumulation in the tumor was limited by the enhanced permeation and retention effect and was independent of the presence of a targeting ligand. A surprisingly high accumulation in the lymph nodes (~70% ID/g) was observed. In the 4T1 lymph node metastasis model, the capability of intravenously injected 111In-LCP to visualize the size-enlarged and tumor-loaded sentinel lymph node was demonstrated. By analyzing the SPECT/CT images taken at different time points, the PK profiles of 111In-LCP in the blood and major organs were determined. The results indicated that the decrement of 111In-LCP blood concentration was not due to excretion, but to tissue penetration, leading to lymphatic accumulation. Larger LCP (diameter ~65 nm) nanoparticles were also prepared for the purpose of comparison. Results indicated that larger LCP achieved slightly lower accumulation in the tumor and lymph nodes, but much higher accumulation in the liver and spleen; thus, larger nanoparticles might not be favorable for imaging purposes. We also demonstrated that LCP with a diameter of ~25 nm were better able to penetrate into tissues, travel in the lymphatic system and preferentially accumulate in the lymph nodes due to 1) small size, 2) a well-PEGylated lipid surface, and 3) a slightly negative surface charge. The ability of ~25 nm LCP to deliver genes to the lymph nodes via IV injection was illustrated by RFP cDNA expression. The results promise the potential use of LCP nanoparticles as formulations for the multifunctional, systemic delivery of both imaging and therapeutic agents to both tumors and lymph nodes.
- Date of publication
- May 2013
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Huang, Leaf
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 2013
- Language
- Publisher
Relations
- Parents:
This work has no parents.