Optimizing the structure of drug delivery systems can help target cancer cells

The main culprit in cancer is healthy cells that have gone wrong and are gaining the ability to divide uncontrollably.

These cells gain growth benefits over normal cells and manipulate the environment by altering the cell pathways involved in growth and metabolism. Over the past few decades, altered pathways and proteins have been identified as targets for therapeutic interventions.

However, what remains challenging is the selective targeting of cancer cells and ensuring that the drug reaches the tumor in appropriate amounts, without significantly affecting normal cells. And in this regard, biocompatible delivery vehicles (which are non-toxic to normal cells) can be useful.

One such candidate is “porphyrins,” a group of organic cyclic compounds that are the mediators of action of several proteins in the human body. Porphyrins are known for their “photosensitizing” effects, i.e., their ability to release reactive oxygen species on light stimulation.

It is these reactive species that give porphyrins anticancer activity. Porphyrins have another advantage: structurally, they are made up of four subunits called “pyrrole subunits,” which give them special electronic properties.

These electronic properties, in combination with receptors on cancer cells, enable selective accumulation of porphyrins in cancer cells, thus serving as an efficient drug delivery system. However, the sterile (atomic arrangement) of the porphyrins-bound functional groups favoring the maximum accumulation and circulation of porphyrin-conjugated drugs in cancer cells has not been well studied.

To answer this question, researchers at Tokyo University of Science, Asst among them. Professor Toshifumi Tojo, Mr Koshi Nishida, Assoc. Professor Takeshi Kondo, and Professor Makoto Yuasa, dug deeper into how the structure of porphyrin derivatives can affect tumor accumulation.

Their findings are published in the journal Scientific Reports.

Porphyrins are used as the basic skeleton of new drugs for cancer treatment because of their ability to accumulate in cancer cells. They have different functional group change roles for drug evaluation. It is not clear whether these functions confer different physical properties and membrane permeability. We aimed to examine how these differences affect drug delivery. “

Toshifumi Tojo, Director of Research and Associate Professor, Tokyo University of Science

In their study, the researchers examined the position of the β (third) and meso (middle) groups of action in porphyrins. First, using a breast cancer cell line, they looked at how these functional roles affect time-dependent accumulation in cancer cells, ranging from 2- to 24-hour time points. They found that meso-derivatives accumulated in cells at 3-fold amounts were higher than β-derivatives and that derivatives with smaller functional groups allowed better accumulation than the largest ones.

Next, they examined how these action group roles affect the pathway by which porphyrins enter cancer glands. They found that porphyrin conjugates complex with plasma proteins that enable their transport through endocytic cells. In addition, the fertilizers could spread into the cytoplasm through the cell membrane.

Furthermore, considering the full nature of electrons, porphyrins appear to interact with serum proteins that carry them to the cells.

Thus, the researchers measured how different roles affect the relationship of these porphyrins with serum proteins and how increased relationships may contribute to tumor accumulation. They found that although the meso state improves the intracellular accumulation of porphyrin conjugates, it had little effect on the movement of small action groups into the cell.

Concluding with their conclusions, Dr. Tojo states, “Our study reveals that the altered positioning of a porphyrin action group significantly affects membrane permeability and intracellular tumor accumulation. We hope that our findings will help guide the structural design of novel porphyrin drugs. “

Overall, their study provides insight into how the structure of drug delivery systems such as porphyrins needs to be considered in order to achieve maximum efficacy, in the hope of paving the way for improvements in cancer drug delivery. .