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Photofrin uptake by murine macrophages
M Korbelik1, G Krosl, D J Chaplin
1Cancer Imaging, British Columbia Cancer Research Centre, Vancouver, Canada.
Abstract:
The uptake of Photofrin by murine peritoneal macrophages in vivo and in vitro was examined. Cellular Photofrin content was measured either by performing a fluorometric assay or by using 14C-labeled drug. For comparison, the uptake of Photofrin by murine SCCVII tumor cells (squamous cell carcinoma) was also examined under the same conditions. The data demonstrate that macrophages have a much greater capacity for Photofrin uptake than SCCVII tumor cells. Photofrin contents at 24 h after drug administration (25 mg/kg) measured 420 +/- 90 (SD), 74 +/- 15, and 15 +/- 2 ng/micrograms of cell protein for peritoneal macrophages, tumor-associated macrophages, and SCCVII tumor cells, respectively. Factors that modify macrophage activity also influence the uptake of the drug by macrophages. The results support the assumption that Photofrin uptake by macrophages is dominated by phagocytosis of highly aggregated components of the drug. In vivo accumulated Photofrin material in peritoneal macrophages, tumor-associated macrophages, and tumor cells has shown very similar in vitro clearance from all three cell types. Only 20-30% of Photofrin was lost from the cells during the initial 24 h, mainly between 1 and 4 h of clearance incubation.
Insights
Murine macrophages exhibit significantly higher Photofrin uptake than SCCVII tumor cells, suggesting phagocytosis of aggregated drug components drives this accumulation. Macrophage activity influences this process.
Area of Science:
- Photodynamic therapy
- Cellular pharmacology
- Immunology
Background:
- Photofrin is a photosensitizer used in photodynamic therapy.
- Understanding drug uptake in different cell types is crucial for optimizing therapeutic efficacy.
- Macrophages play a role in the tumor microenvironment and drug distribution.
Purpose of the Study:
- To investigate the uptake of Photofrin by murine peritoneal macrophages and SCCVII tumor cells.
- To compare the uptake capacity of macrophages versus tumor cells.
- To explore factors influencing Photofrin uptake by macrophages.
Main Methods:
- In vivo and in vitro experiments were conducted.
- Cellular Photofrin content was quantified using fluorometric assays and 14C-labeled drug.
- Murine peritoneal macrophages, tumor-associated macrophages, and SCCVII tumor cells were analyzed.
Main Results:
- Macrophages demonstrated substantially greater Photofrin uptake compared to SCCVII tumor cells.
- At 24 hours post-administration, peritoneal macrophages showed 420 ng/µg protein, tumor-associated macrophages 74 ng/µg, and SCCVII cells 15 ng/µg.
- Macrophage activity significantly influenced drug uptake, supporting a phagocytosis-driven mechanism for aggregated Photofrin.
Conclusions:
- Macrophages possess a higher capacity for Photofrin uptake than SCCVII tumor cells.
- Phagocytosis of aggregated Photofrin components is likely the primary mechanism of uptake by macrophages.
- Photofrin clearance from macrophages and tumor cells in vitro showed similar rates, with most loss occurring within the first 24 hours.