Cellular uptake of rose bengal is mediated by OATP1B1/1B3 transporters.

Due to its fluorescent properties and high yield of singlet oxygen, rose bengal (RB) is one of the most promising photosensitizers for cancer treatment. However, the negative charge of RB molecule may significantly hamper its intracellular delivery by passive diffusion through the cell membrane. Thus, specific membrane protein transporters may be needed. The organic anion transporting polypeptides (OATPs) are a well-characterized group of membrane protein transporters, responsible for cellular uptake of a number of drugs. To our knowledge, this is the first study that evaluates cellular transport of RB mediated by the OATP transporter family. First, electrified liquid-liquid interface, together with biophysical analysis and molecular dynamics simulations were used to characterize the interaction of RB with several models of a cellular membranes. These experiments proved that RB interacts only with the membrane's surface, without spontaneously crossing the lipid bilayer. Evaluation of intracellular uptake of RB by flow cytometry and confocal microscopy showed significant differences in uptake between liver and intestinal cell line models differing in expression of OATP transporters. The use of specific pharmacological inhibitors of OATPs, together with Western blotting and in silico analysis, indicated that OATPs are crucial for cellular uptake of RB.

pH-stable polymersome as nanocarrier for post-loaded rose bengal in photodynamic therapy.

Photodynamic therapy is one of the best alternatives to chemo-, radio- or surgical therapy, as it is noninvasive and causes no severe side effects. The mechanism of photodynamic therapy involves activation of the drug (photosensitizer) with light of appropriate wavelength, which combined with molecular oxygen, leads to production of reactive oxygen species. This starts a cascade of reactions leading to cell death. Thus, the efficiency of this therapy is based mainly on the properties of a photosensitizer, including singlet oxygen yield and accumulation in the tumor area. Current research is aimed at applying nanosystems for the improvement of availability and photodynamic properties of photosensitizers. In order to improve the activity and increase photodynamic potential of rose bengal, one of the most promising drugs in anticancer photodynamic therapy, several drug delivery systems were developed. Among them, polymersomes represent a group of innovative polymeric vesicles mimicking membranous cell structures. Polymersomes are nanosystems made of amphiphilic block copolymers, possessing a spherical, liposome-like architecture. Within this study we present biophysical and in vitro biological characterization of this novel pH-stable nanosystem, which due to the improvement of singlet oxygen and reactive oxygen species (ROS) production by rose bengal is a good candidate for nanocarrier in photodynamic therapy.