title: Functionalization of strongly interacting magnetic nanocubes with (thermo)responsive coating and their application in hyperthermia and heat-triggered drug delivery.
abstract: 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.
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Hamilton
authors.initials: H
authors.lastname: Kakwere
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Manuel Pernia
authors.initials: MP
authors.lastname: Leal
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Materia
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Curcio
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Pablo
authors.initials: P
authors.lastname: Guardia
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Niculaes
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marotta
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.|‡King Abdullah University of Science and Technology (KAUST), BESE division, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falqui
authors.affiliation: †Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pellegrino
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D003131:Combined Modality Therapy / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use* / Q000648:ultrastructure; D008422:Materials Testing; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D058185:Magnetite Nanoparticles; D011108:Polymers; D004317:Doxorubicin
keywords: cubic magnetic nanoparticles; drug release; hyperthermia; pH-responsive; smart materials; thermoresponsive