RT Journal Article T1 Clickable polymer ligand-functionalized iron oxide nanocubes: A promising nanoplatform for 'local hot spots' magnetically triggered drug release A1 Mai, Binh T. A1 Conteh, John S. A1 Gavilán, Helena A1 Girolamo, Alessandro Di A1 Pellegrino, Teresa AB Exploiting the local heat on the surface of magnetic nanoparticles (MNPs) upon exposure to an alternating magnetic field (AMF) to cleave thermal labile bonds represents an interesting approach in the context of remotely triggered drug delivery. Here, taking advantages of a simple and scalable two-step ligand exchange reaction, we have prepared iron oxide nanocubes (IONCs) functionalized with a novel multifunctional polymer ligand having multiple catechol moieties, furfuryl pendants, and polyethylene glycol (PEG) side chains. Catechol groups ensure a strong binding of the polymer ligands to the IONCs surface, while the PEG chains provide good colloidal stability to the polymer-coated IONCs. More importantly, furfuryl pendants on the polymer enable to click the molecules of interest (either maleimide–fluorescein or maleimide–doxorubicin) via a thermal labile Diels–Alder adduct. The resulting IONCs functionalized with a fluorescein/doxorubicin-conjugated polymer ligand exhibit good colloidal stability in buffer saline and serum solution along with outstanding heating performance in aqueous solution or even in viscous media (81% glycerol/water) when exposed to the AMF of clinical use. The release of conjugated bioactive molecules such as fluorescein and doxorubicin could be boosted by applying AMF conditions of clinical use (16 kAm–1 and 110 kHz). It is remarkable that the magnetic hyperthermia-mediated release of the dye/drug falls in the concentration range 1.0–5.0 μM at an IONCs dose as low as 0.5 gFe/L and at no macroscopical temperature change. This local release effect makes this magnetic nanoplatform a potential tool for drug delivery with remote magnetic hyperthermia actuation and with a dose-independent action of MNPs. PB ACS Publications SN 1944-8244 YR 2022 FD 2022-11-02 LK https://hdl.handle.net/10016/37331 UL https://hdl.handle.net/10016/37331 LA eng NO This work was partially supported by the Marie Sklodowska-Curie Innovative training network MSCA-ITN-ETN (HeatNMof project, GA 860942), partially by the AIRC Foundation (AIRC IG-14527 to T.P.), partially by the European Research Council (starting grant ICARO, Contract No. 678109), and partially by ERC proof of concept Hypercube, Contract No. 899661). DS e-Archivo RD 1 jul. 2024