A team of biologists analysed available methods of targeted drug delivery to malignant tumours.

Individual approaches to cancer therapy limit the influence of drugs on healthy tissues and reduce side effects.

The results of the study were published in the journal Cancers. 

The difference between healthy tissue and a tumour lie in the structure of its vasculature and changes in metabolism.

In tumours, blood vessels are formed chaotically, have different shapes and diameters, and exhibit closed ends and protrusions.

The structure of lymphatic vessels also changes.

A tumour and its vasculature grow at different speed causing oxygen and nutrients deficiency.

The structure of the tissue and its metabolism changes, as well as the profile of molecules on the surface of tumour cells, and cancer progression.

Taking these facts into consideration, one can develop methods of target antitumour drugs delivery without affecting healthy cells and causing unnecessary side effects.

Currently, there are three main ways of targeted drug-to-tumour delivery: passive targeting that takes into account the structure of the vessels; active targeting in which an antitumour drug binds with a molecular target; and cell-mediated targeting.

Due to the peculiarities of tumour vessels, large molecules can enter them relatively easily and accumulate in the tumour tissue.

This phenomenon is known as enhanced permeability and retention effect, and passive drug targeting is based on it.

However, this delivery method doesn't always guarantee a desired effect

To increase its efficiency, individual therapies are developed on the basis of tumour characteristics.

For example, the size of an agent may be optimised accordingly.

Active targeting complements the passive method.

It increases the accumulation of a drug in tumour and the time of its retention.

In their earlier work, the team presented a multifunctional complex that leads to a synergistic effect of combined chemo- and radiotherapy agents.

The base of the complex is a luminescent nanoparticle that contains a radioactive isotope 90Y used in radionuclide therapy.

On the surface, there is a bound highly active fragment of exotoxin A obtained from Pseudomonas aeruginosa (PE40).

The complex binds with a marker protein of cancer cells, and its toxic agents affect the tumour.

This treatment method works because tumour cells have different metabolism and molecular profiles than the cells of healthy tissues.

Certain types of cells are able to penetrate tumour tissues and therefore can also be used to deliver drugs.

Cell-mediated targeting extends the washout period, controls the release of the drug, and reduces general toxicity and side effects.

This method has its limitations, but it is also very promising.

"Having a choice between various treatment methods that take into account molecular and structural characteristics of a tumour and being able to adjust drug administration regime means approaching the goals of personalised medicine," said Irina Balalayeva, a Candidate of Biological Sciences, Dean of the Department of Biophysics of the Institute of Biology and Biomedicine at Lobachevsky University, and a senior research associate of the laboratory of nanotheranostics at the Institute of Molecular Medicine, Sechenov Moscow State Medical University.

Understanding the processes of nutrients and metabolic products transportation within a tumour, the peculiarities of its structure, and its interaction with immune system cells can help increase the efficiency of antitumour drug delivery and cancer treatment.

Source: Sechenov University