(6as) A Polymeric Reactor for the Synthesis of Superparamagnetic-Thermal Treatment of Breast Cancer

Research interest: Engineered superparamagnetic iron oxide nanoparticles (SPIONs)

Teaching interest: Nanomedicine

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) have been studied extensively for their localized homogeneous heat generation in breast cancer therapy. However, challenges such as aggregation and inability to produce sub- 10nm SPIONs limit their potential in magneto-thermal ablation. We report a facile, efficient, and roboust in situ method for the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) within polyethylene glycol (PEG) reactor adsorbed onto reduced graphene oxide nanosheets (rGO) via microwave hydrothermal route. This promising modality yields crystalline, stable, biocompatible, and superparamagnetic PEGylated SPION-rGO nanocomposites (NCs) with uniform dispersibility. Our findings show that rGO acts as a breeding ground for the spatially distributed nano-sites around which the ferrihydrite seeds accumulate to ultimately transform into immobilized SPIONs. PEG, in parallel, acts as a critical confining agent physically trapping the accumulated seeds to break down their aggregation and create multiple domains on rGO for the synthesis of quantum-sized SPIONs (9±1 nm in diameter). This dual functionality (rGO & PEG) exhibits a pronounced effect on reducing both the aggregation and the sizes of fabricated SPIONs as confirmed by the STEM images. Toxicity studies indicate that PEGylated SPION-rGO NCs are more biocompatible than PEGylated SPIONs showing no significant induction of cell apoptosis, mitochondrial membrane injury, or oxidative stress. Significantly less lactate dehydrogenase (LDH) release, and hence less necrosis, is observed after 48 hr exposure to high doses of PEGylated SPION-rGO NCs compared with PEGylated SPIONs. NCs induce local heat generation reaching up to 43°C causing significant MCF-7 breast tumor cell ablation of about 68% upon applying an alternating magnetic field.