TY  - JOUR
A1  - Bauer, Tobias A.
A1  - Horvat, Natalie
A1  - Marques, Oriana
A1  - Chocarro, Sara
A1  - Mertens, Christina
A1  - Colucci, Silvia
A1  - Schmitt, Sascha
A1  - Carrella, Luca M.
A1  - Winzen, Svenja
A1  - Koynov, Kaloian
A1  - Fenaroli, Federico
A1  - Blümler, Peter
A1  - Jung, Michaela
A1  - Sotillo, Rocio
A1  - Hentze, Matthias W.
A1  - Muckenthaler, Martina
A1  - Barz, Matthias
T1  - Core cross-linked polymeric micelles for specific iron delivery: inducing sterile inflammation in macrophages
T2  - Advanced healthcare materials
N2  - 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.
KW  - cross-linking
KW  - iron metabolism
KW  - macrophage polarization
KW  - polymeric micelle
KW  - polypept(o)ide
KW  - superparamagnetic iron oxide nanoparticles
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72290
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-722909
SN  - 2192-2659
VL  - 10
IS  - 19, art. 2100385
SP  - 1
EP  - 13
PB  - Wiley-VCH
CY  - Weinheim
ER  -