Cited by 82Photodynamic Therapy Research StudiesPorphyrin Metabolism and DisordersNanoplatforms for cancer theranostics

The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic therapy in bladder cancer cells in vitro

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Wyld, L, Reed, MWR, Brown, NJ·1998·British Journal of Cancer

Abstract

Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.

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Crossref · 10.1038/bjc.1998.265

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  • Other parameters that affect PpIX accumulation include pH, oxygen availability, illumination conditions, or thickness of stratum corneum.

    “Other parameters that affect PpIX accumulation include pH [63,64,65], oxygen availability [63,66], illumination conditions, or thickness of striatum corneum [67].”

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Authors
Wyld, L., Reed, M., & Brown, N.
Affiliations
Royal Hallamshire Hospital (GB)
ORCID
Wyld, L
Venue
British Journal of Cancer
Published
1998-05
Volume
77
Issue
10
Pages
1621-1627
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
OpenAlex
W2030168336
Cited by
82
References
32
Citations by year
2025: 1 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 10 · 2014: 3 · 2013: 4 · 2012: 2
FWCI
4.03
Type
journal article
Language
en
Open access
Locations
  • British Journal of Cancer (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
photodynamic therapy, aminolaevulinic acid, protoporphyrin IX, hypoxia, tumor acidosis, bladder cancer cells, photosensitizer synthesis, heme biosynthesis, oxygen partial pressure, pH
MeSH terms
Acidosis, Aminolevulinic Acid, Urinary Bladder Neoplasms, Cell Survival, Humans, Hydrogen-Ion Concentration, Photochemotherapy, Protoporphyrins, Tumor Cells, Cultured, Cell Hypoxia, Photosensitizing Agents

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