Issue 15, 2023

Ultrasmall superparamagnetic iron oxide nanoparticles for enhanced tumor penetration


The intrinsic pathological characteristics of tumor microenvironments restrict the deep penetration of nanomedicines by passive diffusion. Magnetophoresis is a promising strategy to improve the tumor penetration of nanomedicines aided by the external magnetic propulsive force. However, the research thus far has been focused on large nanoparticles, while ultrasmall superparamagnetic iron oxide (Fe3O4) nanoparticles (<∼20 nm) exhibit better performance in many applications such as cancer diagnosis and treatment. Herein, we aim to determine and understand the penetration of ultrasmall Fe3O4 nanoparticles with various sizes, shapes, surface charges and magnetizations in a 3D tumor spheroid model. The behaviour of the nanoparticles of three sizes (10, 15 and 21 nm), two shapes (spherical and octahedral), and opposite surface charges (negative and positive) was investigated. The results demonstrate that magnetically directed penetration works effectively on ultrasmall Fe3O4 nanoparticles. In the absence of a magnetic field, the shape and the surface charge of the ultrasmall magnetic nanoparticles have a more pronounced effect on their penetration compared to their dimensions. While in the presence of a magnetic field, the advantage of larger magnetic nanoparticles was obvious because they experience higher magnetic driving force due to their higher magnetic moments. Overall, relatively large (21 nm), spherical, and positively charged ultrasmall Fe3O4 nanoparticles showed greater penetration in tumors under a magnetic field. Furthermore, our findings suggest that the penetration efficiency of Fe3O4 nanoparticles is closely related to their cellular internalization ability. Therefore, optimization of the cellular uptake and of the magnetization of magnetic nanoparticles should be considered simultaneously for maximizing their penetration in tumor tissue through magnetophoresis.

Graphical abstract: Ultrasmall superparamagnetic iron oxide nanoparticles for enhanced tumor penetration

Supplementary files

Article information

Article type
01 Dec 2022
02 Mar 2023
First published
03 Mar 2023
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2023,11, 3422-3433

Ultrasmall superparamagnetic iron oxide nanoparticles for enhanced tumor penetration

X. Feng, Y. Xue, S. Gonca, K. Ji, M. Zhang, F. R. García-García, Q. Li, Y. Huang, K. V. Kamenev and X. Chen, J. Mater. Chem. B, 2023, 11, 3422 DOI: 10.1039/D2TB02630A

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