18F-Radiolabeling and In Vivo Analysis of SiFA-Derivatized Polymeric Core-Shell Nanoparticles.

Nanoparticles represent the most widely studied drug delivery systems targeting cancer. Polymeric nanoparticles can be easily generated through a microemulsion polymerization. Herein, the synthesis, radiolabeling, and in vivo evaluation of nanoparticles (NPs) functionalized by an organosilicon fluoride acceptor (SiFA) are reported which can be radiolabeled without further chemical modifications. Four nanoparticles in the sub-100 nm range with distinct hydrodynamic diameters of 20 nm (NP1), 33 nm (NP2), 45 nm (NP3), and 72 nm (NP4), respectively, were synthesized under size-controlled conditions. The SiFA-labeling building block acted as an initiator for the polymerization of polymer P1. The nanoparticles were radiolabeled with fluorine-18 (18F) through simple isotopic exchange (IE) and analyzed in vivo in a murine mammary tumor model (EMT6). The facile 18F radiolabeling SiFA methodology, performed in ethanol under mild reaction conditions, gave radiochemical yields (RCYs) of 19-26% and specific activities (SA) of 0.2-0.3 GBq/mg. Based on preclinical PET analysis, the tumor uptake and clearance profiles were analyzed depending on particle size. The nanoparticle size of 33 nm showed the highest tumor accumulation of SUVmean 0.97 (= 4.4%ID/g) after 4 h p.i. through passive diffusion based on the Enhanced Permeability and Retention (EPR) effect. Overall, this approach exhibits a simple, robust, and reliable synthesis of 18F radiolabeled polymeric nanoparticles with a favorable in vivo evaluation profile. This approach represents a straightforward synthetically accessible alternative to produce radiolabeled nanoparticles without any further surface modification to attach a radioisotope.

Antimicrobial poly(2-methyloxazoline)s with bioswitchable activity through satellite group modification.

Biocides are widely used for preventing the spread of microbial infections and fouling of materials. Since their use can build up microbial resistance and cause unpredictable long-term environmental problems, new biocidal agents are required. In this study, we demonstrate a concept in which an antimicrobial polymer is deactivated by the cleavage of a single group. Following the satellite group approach, a biocidal quaternary ammonium group was linked through a poly(2-methyloxazoline) to an ester satellite group. The polymer with an octyl-3-propionoate satellite group shows very good antimicrobial activity against Gram-positive bacterial strains. The biocidal polymer was also found to have low hemotoxicity, resulting in a high HC50 /MIC value of 120 for S. aureus. Cleaving the ester satellite group resulted in a 30-fold decrease in antimicrobial activity, proving the concept valid. The satellite group could also be cleaved by lipase showing that the antimicrobial activity of the new biocidal polymers is indeed bioswitchable.