Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge
Preclinical studies have demonstrated that nanoparticles (NPs) hold significant potential for advancing cancer therapy by enhancing therapeutic efficacy while reducing side effects. Their effectiveness in solid tumors is, however, often constrained by insufficient accumulation and penetration. Under...
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Frontiers Media S.A.
2025-01-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1520078/full |
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author | Pierre Cybulski Maria Bravo Maria Bravo Jim Jui-Kai Chen Indra Van Zundert Sandra Krzyzowska Farsai Taemaitree Hiroshi Uji-i Hiroshi Uji-i Hiroshi Uji-i Johan Hofkens Johan Hofkens Susana Rocha Beatrice Fortuni |
author_facet | Pierre Cybulski Maria Bravo Maria Bravo Jim Jui-Kai Chen Indra Van Zundert Sandra Krzyzowska Farsai Taemaitree Hiroshi Uji-i Hiroshi Uji-i Hiroshi Uji-i Johan Hofkens Johan Hofkens Susana Rocha Beatrice Fortuni |
author_sort | Pierre Cybulski |
collection | DOAJ |
description | Preclinical studies have demonstrated that nanoparticles (NPs) hold significant potential for advancing cancer therapy by enhancing therapeutic efficacy while reducing side effects. Their effectiveness in solid tumors is, however, often constrained by insufficient accumulation and penetration. Understanding how the physicochemical properties of NPs – such as size, shape, and surface charge – influence their interaction with cells within the tumor is critical for optimizing NP design. In this study, we addressed the challenge of inconsistent NP behavior by systematically evaluating NP uptake in both 2D and 3D tumor models, and NP penetration in spheroids. Our results showed that larger NPs exhibited higher internalization rates in 2D models but limited penetration in 3D spheroids. Furthermore, negatively charged NPs consistently achieved superior accumulation and deeper penetration than neutral and positively charged NPs. Spherical NPs outperformed rod-shaped NPs in tumor accumulation and penetration. These findings underscore the importance of carefully tailoring NP properties to the complex tumor microenvironment for improved therapeutic outcomes in real tumors. |
format | Article |
id | doaj-art-47c67917ff3f4bf4b22f6859a812b887 |
institution | Kabale University |
issn | 2296-634X |
language | English |
publishDate | 2025-01-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cell and Developmental Biology |
spelling | doaj-art-47c67917ff3f4bf4b22f6859a812b8872025-01-24T07:13:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.15200781520078Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface chargePierre Cybulski0Maria Bravo1Maria Bravo2Jim Jui-Kai Chen3Indra Van Zundert4Sandra Krzyzowska5Farsai Taemaitree6Hiroshi Uji-i7Hiroshi Uji-i8Hiroshi Uji-i9Johan Hofkens10Johan Hofkens11Susana Rocha12Beatrice Fortuni13Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumARC Centre of Excellence in Exciton Science, School of Chemistry University of Melbourne, Parkville, VIC, AustraliaMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumResearch Institute for Electronic Science, Hokkaido University, Sapporo, JapanMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumResearch Institute for Electronic Science, Hokkaido University, Sapporo, JapanInstitute for Integrated Cell-Material Science (WPI-iCeMS), Kyoto University, Kyoto, JapanMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumMax Planck Institute for Polymer Research, Mainz, GermanyMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumMolecular Imaging and Photonics, Department of Chemistry, KU Leuven, Leuven, BelgiumPreclinical studies have demonstrated that nanoparticles (NPs) hold significant potential for advancing cancer therapy by enhancing therapeutic efficacy while reducing side effects. Their effectiveness in solid tumors is, however, often constrained by insufficient accumulation and penetration. Understanding how the physicochemical properties of NPs – such as size, shape, and surface charge – influence their interaction with cells within the tumor is critical for optimizing NP design. In this study, we addressed the challenge of inconsistent NP behavior by systematically evaluating NP uptake in both 2D and 3D tumor models, and NP penetration in spheroids. Our results showed that larger NPs exhibited higher internalization rates in 2D models but limited penetration in 3D spheroids. Furthermore, negatively charged NPs consistently achieved superior accumulation and deeper penetration than neutral and positively charged NPs. Spherical NPs outperformed rod-shaped NPs in tumor accumulation and penetration. These findings underscore the importance of carefully tailoring NP properties to the complex tumor microenvironment for improved therapeutic outcomes in real tumors.https://www.frontiersin.org/articles/10.3389/fcell.2024.1520078/fullnanoparticles3D cell modelstumor penetration and accumulationnanoparticle uptakenanoparticle sizenanoparticle shape |
spellingShingle | Pierre Cybulski Maria Bravo Maria Bravo Jim Jui-Kai Chen Indra Van Zundert Sandra Krzyzowska Farsai Taemaitree Hiroshi Uji-i Hiroshi Uji-i Hiroshi Uji-i Johan Hofkens Johan Hofkens Susana Rocha Beatrice Fortuni Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge Frontiers in Cell and Developmental Biology nanoparticles 3D cell models tumor penetration and accumulation nanoparticle uptake nanoparticle size nanoparticle shape |
title | Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge |
title_full | Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge |
title_fullStr | Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge |
title_full_unstemmed | Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge |
title_short | Nanoparticle accumulation and penetration in 3D tumor models: the effect of size, shape, and surface charge |
title_sort | nanoparticle accumulation and penetration in 3d tumor models the effect of size shape and surface charge |
topic | nanoparticles 3D cell models tumor penetration and accumulation nanoparticle uptake nanoparticle size nanoparticle shape |
url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1520078/full |
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