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Cited by 95Nanoparticle-Based Drug DeliveryBarrier Structure and Function StudiesAngiogenesis and VEGF in Cancer

Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability into the tumor microenvironment

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Yokoi, Kenji, Kojic, Milos, Milosevic, Miljan, Tanei, Tomonori, Ferrari, Mauro, Ziemys, Arturas·2014·Cancer Research
DOI 10.1158/0008-5472.can-13-3494PMC PMC4134692
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Abstract

The capillary wall is the chief barrier to tissue entry of therapeutic nanoparticles, thereby dictating their efficacy. Collagen fibers are an important component of capillary walls, affecting leakiness in healthy or tumor vasculature. Using a computational model along with in vivo systems, we compared how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome (DOX-PLD) in tumor vasculature. We found a direct correlation between the collagen content around a tumor vessel to the permeability of that vessel permeability to DOX-PLD, indicating that collagen content may offer a biophysical marker of extravasation potential of liposomal drug formulations. Our results also suggested that while pharmacokinetics determined the delivery of DOX and DOX-PLD to the same tumor phenotype, collagen content determined the extravasation of DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper view into how nanotherapeutics cross biological barriers, possibly helping explain the balance between biological and physical aspects of drug delivery. Cancer Res; 74(16); 4239–46. ©2014 AACR.

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  • Prior studies suggest that tumor permeability and nanoparticle size are critically important for nanoparticle drug distribution to tumors and resulting anticancer effects.

    “This conclusion is consistent with the prior studies suggesting that the tumor permeability as the well as the size of the nanoparticles (including polymeric micelles of different type) are critically important for nanoparticle drug distribution to tumors and the resulting anticancer effects [36–38].”

    From Co-delivery of Paclitaxel and Cisplatin in Poly(2-oxazoline) Polymeric Micelles: Implications for Drug Loading, Release, Pharmacokinetics and Outcome of Ovarian and Breast Cancer Treatments (2019) · cites this paper as [38]

    The Introduction links particle size to tumor accumulation and drug payload, while the Discussion describes size-dependent passage through tumor-vessel collagen. The Results on cell proliferation also link drug extravasation to an anticancer effect. The paper studies liposomes, however, and does not establish the parenthetical claim about different types of polymeric micelles. (LLM, conf=0.83)

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Research works printed but not linked: 1

  1. [34]Kojic M Ziemys A Milosevic M Isailovic V Kojic N Rosic M Transport in biological systems Journal of the Serbian Society for Computational Mechanics/Vol 2011 5 101 128 PMC5957499 29782608

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Authors
Yokoi, K., Kojic, M., Milosevic, M., Tanei, T., Ferrari, M., & Ziemys, A.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • 1The Houston Methodist Research Institute;
  • 3Belgrade Metropolitan University, Research and Development Center for Bioengineering, Kragujevac, Serbia
  • Houston Methodist Research Institute (US)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2014-08-13
Volume
74
Issue
16
Pages
4239-4246
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-13-3494
PMC
PMC4134692
OpenAlex
W2066796083
Cited by
95
References
49
Citations by year
2026: 2 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 8 · 2021: 3 · 2020: 10 · 2019: 8 · 2018: 14 · 2017: 7 · 2016: 8 · 2015: 10
FWCI
3.15
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (U54CA151668, U54CA143837)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
nanoparticle extravasation, PEGylated liposomes, doxorubicin, liposomal chemotherapy, tumor microenvironment, collagen structure, drug diffusion, biophysical markers, nanotherapeutics, tumor heterogeneity
MeSH terms
Animals, Capillaries, Capillary Permeability, Diffusion, Doxorubicin, Female, Liposomes, Mice, Inbred BALB C, Mice, Inbred C57BL, Polyethylene Glycols, Drug Delivery Systems, Collagen Type IV, Mice, Nanoparticles, Tumor Microenvironment

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