Size‐dependent penetration of nanoparticles in tumor spheroids: a multidimensional and quantitative study of transcellular and paracellular pathways
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Date
2023-10-11
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Abstract
Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA‐MB‐231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi‐spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA‐MB‐231 cells and spheroids with or without an energy‐dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two‐photon microscopy, and synchrotron X‐ray fluorescence microscopy. The results reveal that 15 nm nanoparticles penetrate spheroids mainly through an energy‐independent transcellular pathway, while 60 nm nanoparticles penetrate primarily through an energy‐dependent transcellular pathway. Meanwhile, 22 nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site. ©2023 The Authors. Small published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
and is not used for commercial purposes.
Description
Keywords
Nanoparticles, Microscopy, Synchrotrons, Gold, Synthesis, Photons, Medicine
Citation
Chen, W., Wang, W., Xie, Z., Centurion, F., Sun, B., Paterson, D. J., Tsao, S. C.-H., Chu, D., Shen, Y., Mao, G., & Gu, Z. (2024). Size-dependent penetration of nanoparticles in tumor spheroids: a multidimensional and quantitative study of transcellular and paracellular pathways. Small, 20(8), 2304693. doi:10.1002/smll.202304693