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Cited by 82Nanoparticle-Based Drug DeliveryMathematical Biology Tumor GrowthAdvancements in Transdermal Drug Delivery

Effects of hypoxia and nanocarrier size on pH-responsive nano-delivery system to solid tumors

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Soltani, M., Souri, Mohammad, Moradi Kashkooli, Farshad·2021·Scientific Reports
DOI 10.1038/s41598-021-98638-wPMC PMC8481507
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Abstract

One of the special features of solid tumors is the acidity of the tumor microenvironment, which is mainly due to the presence of hypoxic regions. Therefore, pH-responsive drug delivery systems have recently been highly welcomed. In the present study, a comprehensive mathematical model is presented based on extravascular drug release paradigm. Accordingly, drug delivery system using pH-responsive nanocarriers is taken into account to examine the impacts of hypoxic regions as well as the size of nanocarriers for cancerous cell-death. The extent of hypoxic regions is controlled by vascular density. This means that regions with very low vascular density represent regions of hypoxia. Using this mathematical model, it is possible to simulate the extracellular and intracellular concentrations of drug by considering the association/disassociation of the free drug to the cell-surface receptors and cellular uptake. Results show that nanocarriers with smaller sizes are more effective due to higher accumulation in the tumor tissue interstitium. The small size of the nanocarriers also allows them to penetrate deeper, so they can expose a larger portion of the tumor to the drug. Additionally, the presence of hypoxic regions in tumor reduces the fraction of killed cancer cells due to reduced penetration depth. The proposed model can be considered for optimizing and developing pH-sensitive delivery systems to reduce both cost and time of the process.

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  • Tissue damage and lesions in cancer sites make a pro-inflammatory environment that recruits various cells such as mesenchymal stem cells.

    “Tissue damage and lesions in cancer sites make a pro-inflammatory environment that recruits various cells such as MSCs [74–76].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [75]

    The Introduction discusses tumor hypoxia and changes to the extracellular matrix, while Results and discussion > Fluid flow describes pressure and fluid transport in tumors. Searches for mesenchymal stem cells, MSC recruitment, tissue damage, and a pro-inflammatory environment found no passage in our copy addressing the claimed mechanism. (LLM, conf=0.75)

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Authors
Soltani, M., Souri, M., & Moradi Kashkooli, F.
Affiliations
  • University of Waterloo (CA)
  • K. N. Toosi University of Technology (IR)
Corresponding author
Soltani, M.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-09-29
Volume
11
Issue
1
Pages
19350-19350
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-98638-w
PMC
PMC8481507
OpenAlex
W3203685240
Cited by
82
References
6
Citations by year
2026: 9 · 2025: 18 · 2024: 23 · 2023: 17 · 2022: 10 · 2021: 5
FWCI
3.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords
pH-responsive drug delivery, tumor hypoxia, solid tumors, tumor acidosis, vessel density, cell surface receptor binding, cellular uptake, cancer cell death, tumor accumulation
MeSH terms
Tumor Hypoxia, Nanoparticle Drug Delivery System, Antineoplastic Agents, Doxorubicin, Humans, Hydrogen-Ion Concentration, Models, Biological, Neoplasms, Tumor Microenvironment, Drug Liberation

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