Functionalization of strongly interacting magnetic nanocubes with (thermo)responsive coating and their application in hyperthermia and heat-triggered drug delivery

Herein, we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermoresponsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR), but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermoresponsive shell is composed of poly(N-isopropylacrylamide-co-polyethylene glycolmethyl ether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes

A "mix-and-click" approach to double core–shell micelle functionalization

A micellar scaffold formed by self-assembly of a reversible addition–fragmentation chain transfer (RAFT)-synthesized amphiphilic diblock copolymer has been prepared to contain two orthogonal click-compatible functionalities in the core and shell. These functionalities (norbornenes in the core and terminal alkynes in the shell) have been used as handles to modify the micellar assembly in the core using tetrazine–norbornene chemistry or the shell using the copper-catalyzed azide–alkyne reaction. Additionally, both core and shell modifications were carried out in a tandem, one-pot process using the orthogonal chemistries mentioned above. In all cases the reactions were found to be highly efficient, requiring little excess of the modifying small molecule and very simple to perform under ambient conditions