Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines

Abstract

In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications

“…However, rose bengal tends to aggregate in aqueous solutions, which hinders cellular uptake and deteriorates its therapic and imaging performances. [13] Although considerable efforts have been made to increase the water solubility of photosensitizers, developing of anticancer therapy based on PDT-integrated nanoplatforms is still challenging, particularly in an in vivo setting. As a result, it is necessary to develop new photosensitizer-based systems to achieve better therapic performances.…”

“…Meanwhile, rose bengal also possesses the ability to be a fluorescence imaging agent with an excitation wavelength of 575 nm. However, rose bengal tends to aggregate in aqueous solutions, which hinders cellular uptake and deteriorates its therapic and imaging performances . Although considerable efforts have been made to increase the water solubility of photosensitizers, developing of anticancer therapy based on PDT‐integrated nanoplatforms is still challenging, particularly in an in vivo setting.…”

Phosphorhydrazones as Useful Building Blocks for Special Architectures: Macrocycles and Dendrimers

“…Other transfection experiments concerned fluorescein‐labelled oligodeoxyribonucleotide into HeLa cells, and the plasmid inducing an increased GDNF expression (the Glial cell line‐Derived Neurotrophic Factor) into Schwann cells, isolated from sciatic nerves, in view of regenerating transected peripheral nerves in rats . The same dendrimer was used as carrier of a photosensitizer (rose Bengal) to enhance the photodynamic therapy efficiency, a cancer treatment alternative to chemotherapy and radiotherapy . Analogous experiments were carried out with a negatively charged phosphorhydrazone dendrimer and methylene blue .…”

Nanocarriers in photodynamic therapy—in vitro and in vivo studies

“…These reactions lead to direct cytotoxic effects on tumor (Dabrzalska et al, 2017;Vandenbogaerde et al, 1997), damage to the tumor vasculature (Chen, Pogue, Hoopes, & Hasan, 2012), or induction of robust inflammatory responses (Castano, Mroz, Wu, & Hamblin, 2008), leading ultimately to cell death. Three main mechanisms of cell death may be triggered (Mroz, Yaroslavsky, Kharkwal, & Hamblin, 2011;Plaetzer, Kiesslich, Verwanger, & Krammer, 2003) (Figure 4).…”

“…Nowadays many types of light sources are in use or under development, for example, argon/ dye lasers, metal vapor lasers, KTP:YAG/dye lasers, or light-emitting diode (LED) lasers. The second group of light sources includes so-called nonlaser sources in which the light beam can be controlled electronically (Mang, 2004) or by the application of specific filters (Dabrzalska et al, 2017). However, most of the above-mentioned light sources have a serious disadvantage: they are large, which makes them suitable only for external illumination.…”