Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild-type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox-responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.
- Bauer, T. A.
- Horvat, N. K.
- Marques, O.
- Chocarro, S.
- Mertens, C.
- Colucci, S.
- Schmitt, S.
- Carrella, L. M.
- Morsbach, S.
- Koynov, K.
- Fenaroli, F.
- Blümler, P.
- Jung, M.
- Sotillo, R.
- Hentze, M. W.
- Muckenthaler, M. U.
- Barz, M.
Keywords
- cross-linking
- iron metabolism
- macrophage polarization
- polymeric micelle
- polypept(o)ide
- superparamagnetic iron oxide nanoparticles
