Tuning the size and composition of nanohydrogels using a “phantom monomer” for biological applications

We have designed series of monodispersed nanohydrogels (NHG’s) size ranging from 20-400 nm, generated from mixtures of N-isopropylacrylamide, di-block (hydrophilic-hydrophobic) and tri-block (hydrophobic-hydrophilic-hydrophobic) copolymer acrylamide macro-monomer. When the monomers are mixed at high temperature they collapse into well-defined self-assemblies, which can be further polymerized leading to particles with sizes matching the intermediate self-assemblies. The size of the self-assemblies can be tuned/calibrated by combining different ratios of the starting monomers mixtures at high temperature¹.

Herein, we defined the concept of "phantom monomers“ which are the closest structure that mimic a selected monomer but lacks the active function for polymerization. The phantom monomer co-formulated with the other monomers will be present in the intermediate self-assemblies due to their similarity with one of the active monomers, however, upon polymerization, different materials will be generated since the phantom will be excluded due to lack of reactivity. The comparative analyses of the classical systems (first generation) with those obtained with the phantom monomers (second generation) not only put in evidence the self-assembly mediated mechanism, but also prove the generation of new monodispersed NHG’s. The second generation NHG’s were found to be nontoxic based on the XTT assay. We have observed different loading and different phenotypes of the cells treated with the same amounts of DOX-loaded into different NHG’s or free as seen by confocal microscopy.

References

1) Khandadash, R.; Machtey, V.; Sheiner, I.; Gotilied, H.; Gothilf, A.; Ebenstein Y.; Weiss A. and Byk G. Journal of Nanoparticle Research (2014) 16(12), 1-18.