Biodistribution Analysis of NIR-Labeled Nanogels Using in Vivo FMT Imaging in Triple Negative Human Mammary Carcinoma Models.

Abstract

The purpose of this study is to evaluate the biodistribution properties of random-copolymer-based core-cross-linked nanogels of various sizes and surface poly(ethylene glycol) composition. Systematic variations of near-IR labeled nanogels, comprising varying particle sizes (28-135 nm), PEG corona quantity (0-50 mol %), and PEG length (PEG Mn 1000, 2000, and 5000), were prepared and injected in mice that had been subcutaneously implanted with MDA-MB-231-luc-D3H2LN human mammary carcinoma. In vivo biodistribution was obtained using fluorescence molecular tomography imaging at 0, 6, 24, 48, and 72 h postinjection. Retention of total body probe and percentages of total injected dose in the tumor, liver, spleen, lungs, heart, intestines, and kidneys were obtained. Smaller nanogels (∼30-40 nm) with a high PEG conjugation (∼43-46 mol %) of Mn 2000 on their coronas achieved the highest tumor specificity with peak maximum 27% ID/g, a statistically significant propensity toward accumulation with 16.5% ID/g increase from 0 to 72 h of imaging, which constitutes a 1.5-fold increase. Nanogels with greater tumor localization also had greater retention of total body probe over 72 h. Nanogels without extensive PEGylation were rapidly excreted, even at similar sizes to PEGylated nanogels exhibiting whole body retention. Of all tissues, the liver had the highest % ID, however, like other tissues, it displayed a monotonic decrease over time, suggesting nanogel clearance by hepatic metabolism. Ex vivo quantification of individual tissues from gross necropsy at 72 h postinjection generally correlated with the FMT analysis, providing confidence in tissue signal segmentation in vivo. The parameters determined to most significantly direct a nanogel to the desired tumor target can lead to improve effectiveness for nanogels as therapeutic delivery vehicles.

• Authors: Mallory R Gordon, Jiaming Zhuang, Judy Ventura, Longyu Li, Kishore Raghupathi, S Thayumanavan
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 15 Issue 3 Pg. 1180-1191 (03 05 2018) ISSN: 1543-8392 [Electronic] United States
• PMID: 29378144 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line, Tumor
• Female
• Fluorescence
• Humans
• Intravital Microscopy (methods)
• Mice
• Mice, Nude
• Mice, SCID
• Molecular Imaging (methods)
• Nanoparticles (chemistry)
• Particle Size
• Polyethylene Glycols (chemistry, pharmacology)
• Proton Magnetic Resonance Spectroscopy
• Tissue Distribution
• Tomography, Optical (methods)
• Triple Negative Breast Neoplasms (diagnostic imaging, drug therapy)
• Xenograft Model Antitumor Assays