Biodistribution and fate of core-labeled I polymeric nanocarriers prepared by Flash NanoPrecipitation (FNP)

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2016-04, Vol.4 (14), p.2428-2434
• Main Authors: Tang, Christina, Edelstein, Jasmine, Mikitsh, John L, Xiao, Edward, Hemphill, Aaron H, Pagels, Robert, Chacko, Ann-Marie, Prud'homme, Robert
• Format: Article
• Language: English
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c5tb02172c

Non-invasive medical imaging techniques based on radionuclide imaging are powerful platforms to track the fate of radiolabeled materials for diagnostic or drug delivery applications. Polymer-based nanocarriers tagged with non-standard radionuclides with relatively long half-lives ( e.g. 64 Cu: t 1/2 = 12.7 h, 76 Br: t 1/2 = 16.2 h, 89 Zr: t 1/2 = 3.3 d, 124 I: t 1/2 = 4.2 d) may greatly expand applications of nanomedicines in molecular imaging and therapy. However, radiolabeling strategies that ensure stable in vivo association of the radiolabel with the nanocarrier remain a significant challenge. In this study, we covalently attach radioiodine to the core of pre-fabricated nanocarriers. First, we encapsulated polyvinyl phenol within a poly(ethylene glycol) coating using Flash NanoPrecipitation (FNP) to produce stable 75 nm and 120 nm nanocarriers. Following FNP, we radiolabeled the encapsulated polyvinyl phenol with 125 I via electrophilic aromatic substitution in high radiochemical yields (>90%). Biodistribution studies reveal low radioactivity in the thyroid, indicating minimal leaching of the radiolabel in vivo . Further, PEGylated [ 125 I]PVPh nanocarriers exhibited relatively long circulation half-lives ( t 1/2α = 2.9 h, t 1/2β = 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection. Flash NanoPrecipitation provides a facile, scalable platform for producing stable, radiolabeled PEGylated nanocarriers for drug delivery and translational imaging applications.