Size‐dependent penetration of nanoparticles in tumor spheroids: a multidimensional and quantitative study of transcellular and paracellular pathways

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dc.contributor.authorChen, Wen_AU
dc.contributor.authorWang, WQen_AU
dc.contributor.authorXie, Zen_AU
dc.contributor.authorCenturion, Fen_AU
dc.contributor.authorSun, Ben_AU
dc.contributor.authorPaterson, DJen_AU
dc.contributor.authorTsao, SCHen_AU
dc.contributor.authorChu, Den_AU
dc.contributor.authorShen, Yen_AU
dc.contributor.authorMao, Gen_AU
dc.contributor.authorGu, Zen_AU
dc.date.accessioned2024-11-15T04:36:20Zen_AU
dc.date.available2024-11-15T04:36:20Zen_AU
dc.date.issued2023-10-11en_AU
dc.date.statistics2024-11-15en_AU
dc.description.abstractTumor 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.en_AU
dc.description.sponsorshipThe authors acknowledge funding support from UNSW RNA Institute Seed Fund and NSW Cardiovascular Research Capacity Program. Part of this research was undertaken on the X-ray fluorescence microscopy (XFM) beamline at the Australian Synchrotron, part of ANSTO. The authors would like to thank Dr Daryl Howard and Dr Andrew Langendam at Australian Synchrotron ANSTO and Miss Lingqing Zong for their support in X-ray fluorescence microscopy imaging and analysis. The authors would like to acknowledge the facilities and the scientific and technical assistance provided by the Electron Microscope Unit and Microscopy Australia, Katharina Gaus Light Microscopy Facility at UNSW Sydney. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians.en_AU
dc.format.mediumPrint-Electronicen_AU
dc.identifier.articlenumbere2304693en_AU
dc.identifier.citationChen, 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.202304693en_AU
dc.identifier.issn1613-6810en_AU
dc.identifier.issn1613-6829en_AU
dc.identifier.issue8en_AU
dc.identifier.journaltitleSmallen_AU
dc.identifier.urihttps://doi.org/10.1002/smll.202304693en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15762en_AU
dc.identifier.volume20en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherWileyen_AU
dc.subjectNanoparticlesen_AU
dc.subjectMicroscopyen_AU
dc.subjectSynchrotronsen_AU
dc.subjectGolden_AU
dc.subjectSynthesisen_AU
dc.subjectPhotonsen_AU
dc.subjectMedicineen_AU
dc.titleSize‐dependent penetration of nanoparticles in tumor spheroids: a multidimensional and quantitative study of transcellular and paracellular pathwaysen_AU
dc.typeJournal Articleen_AU
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