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.

Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy

“…However, it is worth considering that the delivery of nanoparticles to tumors can be enhanced using external stimuli such as magnetic field gradients. 79 In this regard, inducing the disassembly of the chains into smaller fragments prior to encountering the ECM could serve as a viable solution to overcome the aforementioned obstacle.…”

“…The cross-linking of ECM proteins, a consequence of tumor growth and progression, results in an augmented stiffness or rigidity, − consequently hindering the rotation of the chains within the ECM. However, it is worth considering that the delivery of nanoparticles to tumors can be enhanced using external stimuli such as magnetic field gradients . In this regard, inducing the disassembly of the chains into smaller fragments prior to encountering the ECM could serve as a viable solution to overcome the aforementioned obstacle.…”

Ultrasmall superparamagnetic iron oxide nanoparticles for enhanced tumor penetration

“…Therefore, various magnetic nanorobots/motors/swimmers have been developed to perform different motion patterns under different magnetic field designs [9][10][11] . Beyond passive diffusion, external magnetic field can offer efficient driving force on magnetic nanomedicines to promote their penetration in tumor tissue, and this process also possesses advantages of controllability and programmability [12][13][14][15][16][17][18] .…”

“…[9][10][11] Beyond passive diffusion, an external magnetic field can exert an efficient driving force on magnetic nanomedicines to promote their penetration into tumor tissue, and this process also possesses advantages of controllability and programmability. [12][13][14][15][16][17][18] Iron oxide (Fe 3 O 4 ) nanoparticles are the most commonly used magnetic nanoparticles in biomedicine, and several compositions have been approved for clinical use for magnetic resonance imaging (MRI), iron deficiency treatment, and thermotherapy. [19][20][21] Fe 3 O 4 nanoparticles can be mainly categorized as orally large (B300 nm to 3.5 mm), standard (B40 nm to 150 nm), and ultrasmall (Bo40 nm) nanoparticles.…”

“…9–11 Beyond passive diffusion, an external magnetic field can exert an efficient driving force on magnetic nanomedicines to promote their penetration into tumor tissue, and this process also possesses advantages of controllability and programmability. 12–18…”