“Tandem” nanomedicine approach against osteoclastogenesis: polysulfide micelles synergically scavenge ROS and release rapamycin

Farah El Mohtadi, Richard d’Arcy, Jason Burke, Julio M. Rios De La Rosa, Arianna Gennari, Roberto Marotta, Nora Francini, Robert Donno, Nicola Tirelli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)305-318
Number of pages14
Early online date3 Dec 2019
Publication statusPublished - 10 Feb 2020

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