A pink dye, a beam of light, and molecular trees that carry it

Rose bengal is a pink dye that eye doctors already use as a diagnostic tool. It has a second talent: when light of the right colour hits it, it produces highly reactive forms of oxygen that damage whatever is nearby. Put the dye inside a tumour cell, shine a light, and the cell can be destroyed. This idea, photodynamic therapy, is a real and established approach, used for example against skin cancers. The catch is getting the dye where it needs to be.

A dye that stays on the doorstep

Rose bengal carries a negative charge in the body, which makes it hard for it to pass through the fatty membrane that wraps every cell. It also clears from the body quickly, with a half-life of about 30 minutes, and in solution it tends to clump, which weakens its effect.

In one study we asked how it gets into cells at all. Laboratory measurements and our simulations agreed that rose bengal sits on the surface of a membrane without crossing it on its own. Experiments in liver and intestinal cells then pointed to a family of transport proteins, called OATPs, as the main way in.

Molecular trees

Dendrimers are synthetic molecules that branch out from a central core like a tree, again and again, until they form a small, roughly spherical particle. The ones we studied, called PAMAM and PPI, are covered in positive charges on the outside. Rose bengal is negative, so the two attract.

We simulated each dendrimer surrounded by ten rose bengal molecules. In every case all ten were captured within 16 nanoseconds, and none let go during the 200 nanoseconds that followed. The simulations also showed that PPI dendrimers are more rigid than PAMAM ones, and that the complexes differ in how strongly charged their surface remains once the dye is bound.

Our colleagues in the lab tested the same pairs on three lines of basal cell carcinoma, the most common skin cancer. Every complex was more toxic to the cells under light than rose bengal alone, and none was toxic in the dark. Even the weakest carrier nearly doubled how much dye got inside the cells. The ranking of the carriers matched what the simulations suggested: the complex with the most positive surface delivered the most dye, and the one closest to neutral delivered the least.

Half a tree

Our most recent work looked at dendrons, which are single branches of such a tree. Some of these molecules have one water-loving side and one water-repelling side, and they can assemble on their own into tiny hollow spheres that could carry a drug. Triazine-carbosilane dendrons had already been shown to help rose bengal into cells and to boost its effect under light.

Our simulations showed that the dendrons and rose bengal bind quickly and stay together, held mainly by the attraction between opposite charges, especially in more acidic conditions. How much each dendron flexes and changes shape affected how stable the pair was. Experiments confirmed that the complexes form, and that acidity changes how many dye molecules bind and how much energy is involved.

Why it matters

None of this is a treatment yet. These are studies in cells and in the computer. What they give is a clearer picture of which chemical features make a carrier hold a light-activated drug well, which is the kind of rule that helps chemists design better carriers instead of testing them one by one.

These studies were collaborations with experimental groups at the University of Łódź, Poland, and partners elsewhere in Europe; our part was the molecular simulations.

Read the paper: Zizzi, Sztandera, Gorzkiewicz, Buczkowski, Apartsin, Deriu, Klajnert-Maculewicz, Nanoscale 17(3), 1433–1448 (2025). doi:10.1039/d4nr02335h

Related: Sztandera et al., Journal of Medicinal Chemistry 64(21), 15758–15771 (2021). doi:10.1021/acs.jmedchem.1c01080

Related: Sztandera et al., Bioelectrochemistry 152, 108449 (2023). doi:10.1016/j.bioelechem.2023.108449