TY - JOUR
T1 - “Tandem” nanomedicine approach against osteoclastogenesis: polysulfide micelles synergically scavenge ROS and release rapamycin
AU - El Mohtadi, Farah
AU - d’Arcy, Richard
AU - Burke, Jason
AU - M. Rios De La Rosa, Julio
AU - Gennari, Arianna
AU - Marotta, Roberto
AU - Francini, Nora
AU - Donno, Robert
AU - Tirelli, Nicola
PY - 2020/2/10
Y1 - 2020/2/10
N2 - We show the first example of a synergic approach of oxidant (ROS) scavenging carrier and ROS-responsive drug release in the context of a potential therapy against osteoporosis, aiming to inhibit the differentiation of inflammatory cells into osteoclasts. In our “tandem” approach, a branched amphiphilic, PEGylated polysulfide (PPSES–PEG) was preferred over a linear analogue, because of improved homogeneity in the aggregates (spherical micelles vs mixture of wormlike and spherical), increased stability, and higher drug loading (up to ∼22 wt % of antiosteoclastic rapamycin). These effects are ascribed to the branching inhibiting crystallization in the polysulfide blocks. The ROS-scavenging micelles alone were already able to reduce osteoclastogenesis in a RAW 264.7 model, but the “drug” combination (the polymer itself + rapamycin released only under oxidation) completely abrogated the process. An important take-home message is that the synergic performance depended very strongly on the oxidant: oxidizable group molar ratio, a parameter to carefully tune in the perspective of targeting specific diseases.
AB - We show the first example of a synergic approach of oxidant (ROS) scavenging carrier and ROS-responsive drug release in the context of a potential therapy against osteoporosis, aiming to inhibit the differentiation of inflammatory cells into osteoclasts. In our “tandem” approach, a branched amphiphilic, PEGylated polysulfide (PPSES–PEG) was preferred over a linear analogue, because of improved homogeneity in the aggregates (spherical micelles vs mixture of wormlike and spherical), increased stability, and higher drug loading (up to ∼22 wt % of antiosteoclastic rapamycin). These effects are ascribed to the branching inhibiting crystallization in the polysulfide blocks. The ROS-scavenging micelles alone were already able to reduce osteoclastogenesis in a RAW 264.7 model, but the “drug” combination (the polymer itself + rapamycin released only under oxidation) completely abrogated the process. An important take-home message is that the synergic performance depended very strongly on the oxidant: oxidizable group molar ratio, a parameter to carefully tune in the perspective of targeting specific diseases.
UR - https://research.manchester.ac.uk/en/publications/tandem-nanomedicine-approach-against-osteoclastogenesis-polysulfi
U2 - 10.1021/acs.biomac.9b01348
DO - 10.1021/acs.biomac.9b01348
M3 - Article
SN - 1525-7797
VL - 21
SP - 305
EP - 318
JO - Biomacromolecules
JF - Biomacromolecules
ER -