Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles

Abstract

There has been increased interest in the use of polymeric nanoparticles as carriers for near-infrared (NIR) fluorescence dyes for cancer diagnosis. However, efficient delivery of nanoparticles to the tumors after systemic administration is limited by various biobarriers. In this study, we investigated the pharmacokinetics, biodistribution, and tumor uptake of sub-nanometer sized polymeric nanoparticles (<100 nm in diameter) coated with polyethylene glycol in tumor-bearing mice. To facility our studies, these particles were labeled with gamma emitter indium-111. We found that two NIRF nanoparticles having the same size (~20 nm) and chemical composition but different structures (i.e., hydrogel vs. core-shell nanolatex), or the same core-shell nanolatex particles with different sizes (20, 30, and 60 nm), had different blood circulation times, biodistribution, and tumor uptake. Interestingly, the tumor uptake of the nanolatex particles correlated well with their blood residence times (R 2 = 0.95), but similar correlations were not found between nanogel and nanolatex particles (R 2 = 0.05). These results suggest that both the blood circulation time and the extent of hydration of the nanoparticles play an important role in the tumor uptake of nanoparticles. Prolonged blood circulation of these NIRF nanoparticles allowed clear visualization of tumors with γ-scintigraphy and optical imaging after intravenous administration. A better understanding with regard to how the characteristics of nanoparticles influence their in vivo behavior is an important step towards designing NIRF nanoparticles suitable for molecular imaging applications and for efficient tumor delivery.

A fluorescent chromophore TOTO‐3 as a ‘smart probe’ for the assessment of ultrasound‐mediated local drug delivery in vivo

“…Molecular imaging methods that monitor and quantify nearly real-time the processes of ultrasound-mediated intracellular drug delivery would allow for a direct assessment of the drug internalization and predict the treatment efficacy. In vivo imaging of the distribution of drug carriers and the release of their payload has already been carried out using various imaging techniques, including SPECT (19,20), PET (21), MRI (22,23), ultrasound (24) and fluorescence (25,26). Contrast agents can be coupled to or loaded into drug carriers for these imaging applications without changing their biodistribution (27,28).…”

Polymeric nanoparticles for optical sensing

“…Typically particles with diameter smaller than 100 nm are considered for in vivo applications, to reduce opsonization and assure subsequent clearance. It is however still unclear how variations in the size of NPs within the range from 20 to 100 nm may influence their biodistribution (Yang et al, 2009b). The biodistribution of NPs also depends on their surface properties (Stark, 2011).…”

Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer

“…Many of these probes, however, have limited usefulness in vivo, mainly because of low fluorescence signal amplification and lack of stability under physiological conditions after intravenous injection. Nanoparticle-containing NIR fluorophores, which have shown enhanced stability, improved targeting, and reduced nonspecific binding [15], may be effective in identifying smaller lesions at an earlier stage and may be used for in situ characterization of the identified lesions. These probes may eventually be utilized for the early diagnosis of diseases such as cancer and for monitoring therapeutic efficacy in vivo.…”