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Cited by 169Nanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug DeliveryHydrogels: synthesis, properties, applications

Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models

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Agarwal, Rachit, Jurney, Patrick, Raythatha, Mansi, Singh, Vikramjit, Sreenivasan, Sidlgata. V., Shi, Li, Roy, Krishnendu·2015·Advanced Healthcare Materials
DOI 10.1002/adhm.201500441PMC PMC9346573
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Abstract

Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography‐fabricated, polyethylene‐glycol‐based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor‐like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk‐like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast‐agent delivery.

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  • Penetration is governed by the physicochemical characteristics of the drug or particle-including size, surface charge, shape, lipophilicity, and acid dissociation constant-as well as by the structural and biochemical properties of the spheroid, such as ECM density, extracellular pH gradients, and compactness of the cellular arrangement.

    “Penetration is governed by the physicochemical characteristics of the drug or particle—including size, surface charge, shape, lipophilicity, and acid dissociation constant—as well as by the structural and biochemical properties of the spheroid, such as ECM density, extracellular pH gradients, and compactness of the cellular arrangement [99,206,290].”

    From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [290]

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References 78 · Cited by 169

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Authors
Agarwal, R., Jurney, P., Raythatha, M., Singh, V., Sreenivasan, S. V., Shi, L., & Roy, K.
Affiliations
  • Georgia Institute of Technology (US)
  • The University of Texas at Austin (US)
Corresponding author
  • Agarwal, Rachit
  • Roy, Krishnendu
ORCID
Venue
Advanced Healthcare Materials
Publisher
Wiley
Published
2015-09-16
Volume
4
Issue
15
Pages
2269-2280
ISSN
  • 2192-2640 (ISSN-L)
  • 2192-2659
DOI
10.1002/adhm.201500441
PMC
PMC9346573
OpenAlex
W2105619762
Cited by
169
References
78
Citations by year
2026: 17 · 2025: 17 · 2024: 20 · 2023: 15 · 2022: 16 · 2021: 21 · 2020: 19 · 2019: 14 · 2018: 11 · 2017: 12 · 2016: 7
FWCI
3.62
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Advanced Healthcare Materials (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Texas at Austin
  • Medical Research Council
  • National Institute of Biomedical Imaging and Bioengineering (EB008835, R21EB008835)
  • National Center for Research Resources (S10RR027950)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
nanoparticle penetration, nanoparticle distribution, nanoparticle morphology, aspect ratio, 3D spheroid model, nanogels, polyethylene glycol, cylindrical nanoparticles, nanorods, drug delivery, nanocarrier design
MeSH terms
Humans, Models, Molecular, Neoplasms, Polyethylene Glycols, Spheroids, Cellular, Nanotubes, Nanoparticles, Molecular Imprinting, HEK293 Cells

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