Abstract

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

Highlights

  • Photodynamic therapy (PDT) is an alternative cancer treatment offering a more targeted and less invasive treatment regimen compared to traditional modalities

  • To evaluate the distribution of methylated β-CD (Me-β-CD)-free mTHPC in subpopulations of blood cells, we analyzed the blood incubated with mTHPC by flow cytometry

  • To distinguish red blood cells (RBC) and white blood cells (WBC), the samples were incubated with CD45-FITC antibody (FL1), which

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Summary

Introduction

Photodynamic therapy (PDT) is an alternative cancer treatment offering a more targeted and less invasive treatment regimen compared to traditional modalities. Photodynamic therapy (PDT) employs a combination of the photosensitizer (PS), light, and molecular oxygen to selectively target tumor cells via cytotoxic activity [1]. One of the chief benefits of PDT compared to other cancer treatment modalities is the dual selectivity due to the selective PS accumulation in the target tissue and light delivery in a spatially confined and focused manner [2,3]. Many effective PSs are insoluble hydrophobic molecules tending to aggregate upon systemic administration.

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