The tumor is in sight
Personalized approach in the fight against cancer
Biologists of the I.M. Sechenov First Moscow State Medical University and Lobachevsky University (Nizhny Novgorod) examined the existing methods of targeted drug delivery to the tumor. Cancer treatment methods that provide an individual approach can reduce the impact of drugs on healthy tissues and reduce the side effects of drugs. The research results are published in the journal Cancers (Kutova et al., Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency).
A tumor can be distinguished from healthy tissue by the structure of its vascular network and changes in metabolism. The blood vessels of neoplasms grow chaotically, they have an irregular shape and diameter, blind ends and protrusions appear in them. The structure of the lymphatic vessels is also broken. The tumor and its vascular system grow at different rates, which leads to a lack of oxygen and nutrients. Tissue structure and metabolism change, as well as the profile of molecules on the surface of tumor cells, and cancer progresses. Taking into account such features, it is possible to develop methods for the delivery of antitumor drugs with minimal impact on healthy tissues and with fewer side effects.
Scientists consider three main methods of targeted drug delivery to a neoplasm: passive targeting, which takes into account the features of the structure of blood vessels, active targeting, in which an antitumor drug binds to a molecular target, and cell-mediated targeting of a tumor.
Due to the peculiarities of tumor vessels, large molecules relatively easily penetrate into them and accumulate. This phenomenon is described as the effect of increased permeability and retention, which underlies the passive targeting of an antitumor drug. However, this method of delivery does not always achieve the desired effect. To increase the effectiveness of this method, the treatment is approached individually, based on the characteristics of a particular tumor, for example, optimize the size of the drug carrier.
Active targeting complements passive targeting, with its help they increase the accumulation of the drug in the neoplasm and increase its retention time. In an earlier work, scientists presented a multifunctional complex that allows achieving the mutually reinforcing effect of combined agents for chemo- and radiotherapy. The core of this complex is a luminescent (luminous) nanoparticle. It contains the radioactive isotope 90 Y, which is used for radionuclide therapy, and on the surface there is a highly effective fragment of exotoxin A from the microorganism Pseudomonas aeruginosa (PE40). The complex binds to a protein marker of cancer cells and toxic agents affect the tumor. This method of treatment is possible due to changes in the metabolism and molecular profile of the neoplasm.
Certain types of cells are able to penetrate the tumor tissue, so they can also be used for drug delivery. Cell-mediated targeting allows prolonging the period of drug withdrawal from the tumor, controlling its release and reducing overall toxicity and side effects. This method has its limitations, but also great prospects.
A diagram illustrating the principle of active drug delivery to the tumor. Active delivery implies covalent or non-covalent binding of the delivered agent to a molecule/module that determines its selective interaction with specific molecules on the surface of target cells. The guiding agents can be attached either directly to the delivered drug or to a nanoscale carrier loaded with a therapeutic drug. Boxes I and II show examples of using active delivery.
"The possibility of choosing the most appropriate treatment method that takes into account the molecular and structural features of the tumor and the precise adjustment of the drug administration mode leads us to the ideals of personalized medicine," says Irina Balalaeva, PhD, Associate Professor of Biophysics at the Institute of Biology and Biomedicine of Lobachevsky University, senior researcher at the Nanoteranostics Laboratory of the Institute of Molecular Medicine of the First Sechenov Moscow State Medical University.
Understanding the processes of transport of nutrients and metabolic products inside the tumor, the features of its structure, data on the interaction of the tumor with cells of the immune system will improve the efficiency of the delivery of antitumor drugs and the treatment of oncological diseases.
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