Adding a thin coating of the biocompatible polymer poly(ethylene glycol) (PEG) to the surface of sulfur-modified, or thiolated, nanoparticles designed to fall apart inside tumors, prolongs the time that the resulting nanoparticles remain in tumors.
The resulting nanoparticles also remain in the bloodstream longer than is typical of gelatin nanoparticles, which could have the effect of improving the tumor-targeting properties of these nanoparticles.
Mansoor Amiji, Ph.D., who heads the National Cancer Institute’s Cancer Nanotechnology Platform Partnership at Northeastern University, and graduate student Sushma Kommareddy studied the biodistribution and pharmacokinetic properties of a gelatin-based nanoparticle designed to disintegrate inside tumor cells specifically, both with and without the PEG coating. These investigators added a radioactive tag – 111Indium – to the nanoparticles in order to track their location within the body of mice with human breast tumors. The two researchers reported their work in the Journal of Pharmaceutical Sciences.
After injecting one of four different nanoparticles – gelatin, thiolated gelatin, PEG-coated gelatin, and PEG-coated thiolated gelatin – into the bloodstream of the test animals, the investigators tracked the particles as they circulated through the body and accumulated within the tumors. The nanoparticles, which ranged in size from 230 nanometers in diameter for the gelatin nanoparticles to 329 nanometers in diameter for the PEG-modified gelatin nanoparticles, were all small enough to accumulate within solid tumors by the enhanced permeation and retention effect.
By 12 hours after injection, only about 1 percent of the uncoated nanoparticles remained in circulation, compared to almost 7 percent of either of the two PEG-coated nanoparticles, which had nearly identical pharmacokinetic parameters. More importantly, tumors retained more of the PEG-coated nanoparticles than uncoated nanoparticles. Twelve hours after injection, the investigators recovered 13 percent of the PEG-coated nanoparticles from tumors, compared to 7 percent for the gelatin nanoparticles and 9 percent for the thiolated gelatin nanoparticles. The researchers calculated from their data that PEG-coated thiolated nanoparticles had a five-fold higher half-life in blood than either of the uncoated nanoparticles.
The researchers also noted a progressive increase in radioactivity appearing in the dosed animals’ kidneys. The investigators concluded from these data and others on tissue distribution that the kidneys act as the major excretion route for the nanoparticles.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Biodistribution and pharmacokinetic analysis of long-circulating thiolated gelatin nanoparticles following systemic administration in breast cancer-bearing mice.” This paper was published online in advance of print publication. An abstract is available through PubMed. View abstract.