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BRIEF RESEARCH REPORT article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1520078
This article is part of the Research Topic 3D Models in Cancer Research: Bridging Tumor Biology and Personalized Medicine View all 6 articles

Nanoparticle Accumulation and Penetration in 3D Tumor Models: the Effect of Size, Shape, and Surface Charge

Provisionally accepted
Pierre Cybulski Pierre Cybulski 1Maria Bravo Maria Bravo 1,2Jim Jui-Kai Chen Jim Jui-Kai Chen 1Indra Van Zundert Indra Van Zundert 1Sandra Krzyzowska Sandra Krzyzowska 1Farsai Taemaitree Farsai Taemaitree 3Hiroshi Uji-i Hiroshi Uji-i 1,3,4Johan Hofkens Johan Hofkens 1Susana Rocha Susana Rocha 1*Beatrice Fortuni Beatrice Fortuni 1*
  • 1 Molecular Imaging and Photonics, Chemistry Department, KU Leuven, Leuven, Belgium
  • 2 ARC Centre of Excellence in Exciton Science, School of Chemistry, Faculty of Science, University of Melbourne, Parkville, Victoria, Australia
  • 3 Research Institute for Electronic Science, Hokkaido University, Sapporo, Hokkaidō, Japan
  • 4 Institute for Integrated Cell-Material Science (WPI-iCeMS), Kyoto University, Kyoto, Kyōto, Japan

The final, formatted version of the article will be published soon.

    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 chargeinfluence 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.

    Keywords: Nanoparticles, 3D cell models, Tumor penetration and accumulation, Nanoparticle uptake, Nanoparticle size, Nanoparticle shape, Nanoparticle surface charge, Spheroid models

    Received: 30 Oct 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Cybulski, Bravo, Chen, Van Zundert, Krzyzowska, Taemaitree, Uji-i, Hofkens, Rocha and Fortuni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Susana Rocha, Molecular Imaging and Photonics, Chemistry Department, KU Leuven, Leuven, Belgium
    Beatrice Fortuni, Molecular Imaging and Photonics, Chemistry Department, KU Leuven, Leuven, Belgium

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.