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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Main Authors: Pierre Cybulski, Maria Bravo, Jim Jui-Kai Chen, Indra Van Zundert, Sandra Krzyzowska, Farsai Taemaitree, Hiroshi Uji-i, Johan Hofkens, Susana Rocha, Beatrice Fortuni
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
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.
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institution Kabale University
issn 2296-634X
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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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