Targeting Magnetic Nanoparticles in Physiologically Mimicking Tissue Microenvironment

Abstract

Magnetic nanoparticles as drug carriers, despite showing immense promises in preclinical trials, have remained to be only of limited use in real therapeutic practice primarily due to unresolved anomalies concerning their grossly contrasting controllability and variability in performance in artificial test benches as compared to human tissues. To circumvent the deficits of reported in vitro drug testing platforms that deviate significantly from the physiological features of the living systems and result in this puzzling contrast, here, we fabricate a biomimetic microvasculature in a flexible tissue phantom and demonstrate distinctive mechanisms of magnetic-field-assisted controllable penetration of biocompatible iron oxide nanoparticles across the same, exclusively modulated by tissue deformability, which has by far remained unraveled. Our experiments deciphering the transport of magnetic nanoparticles in a blood analogue medium unveil a decisive interplay of the flexibility of the microvascular pathways, magnetic pull, and viscous friction toward orchestrating the optimal vascular penetration and targeting efficacy of the nanoparticles in colorectal tissue-mimicking bioengineered media. Subsequent studies with biological cells confirm the viability of using localized magnetic forces for aiding nanoparticle penetration within cancerous lesions. We establish nontrivially favorable conditions to induce a threshold force for vascular rupture and eventual target of the nanoparticles toward the desired extracellular site. These findings appear to be critical in converging the success of in vitro trials toward patient-specific targeted therapies depending on personalized vascular properties obtained from medical imaging data.