dos de los tratamientos más efficacious para el cáncer juntos

Researchers at the University of Pittsburgh (USA) have designed nanoparticles that combine two of the most effective treatments for cancer: chemotherapy and immunotherapy. al estudio se ha publicado en «Nature Nanotechnology». Cuando se combinó con un pharmaco de chemotherapy existent y se empaquetó en diminutas nanopartículas, la therapy redujo los tumors en models de ratón con cáncer de colon y de pancreas.

El estudio presenta dos aspectos innovatores. But one side, explained the principal author Song Li, “the discovery of a new therapeutic objective and a new nanocarrier that is very effective in the selective administration of immunotherapy and chemotherapeutic drugs”.

Aunque todavía no sabemos si nuestro enfoque funciona en pacientes, «nuestros finagados suguegen que hay mucho potential», assured.

La chemotherapy es un pilar del tratamiento del cáncer, pero las céluras cancerosas residuales pueden persistir y causar una recaída del tumor. This process involves a lipid called phosphatidylserine (PS), which generally finds itself inside the inner layer of the tumor cell membrane but migrates to the cellular surface in response to chemotherapy medications. On the surface, the PS acts as an immunosuppressor, protecting the remaining cancer cells from the immune system.

In this work, the researchers found that therapy with the chemotherapeutics fluorouracil and oxoplatinum (FuOXP) raised the levels of Xkr8, a protein that controlled the distribution of PS in the cell membrane. This result suggested that the Xkr8 block would prevent the cancer cells from deviating the PS to the cellular surface, allowing the immune cells to eliminate the cancer cells that persisted after chemotherapy.

Los animals treated with nanoparticles that contained as much FuOXP as siRNA had better tumoral microenvironments with more T cells

Another study that was published in “Cell Reports” identified Xkr8 as a new therapeutic objective to boost the antitumoral immune response.

In this work, fragments of genetic code called short interfering RNA (siRNA), which detiene la production of specific proteins, in this case, Xkr8, have been designed. Después de empaquetar siRNA y FuOXP juntos en nanopartículas de doble acción, el siguiente paso fue dirigirlos a los tumors.

Las nanopartículas suelen ser demasiado grandes para cruzar los vasos sanguinos intactos en el tejido sano, pero pueden llegar a las céluras cancerousosas porque los tumors a veces tienen vasos poco desarrollados con agujeros que les permanente el paso. Pero este enfoque directed al tumor es limitado porque muchos humano tumors no tienen agujeros lo suficiente grandes para que pasen las nanopartículas.

“Al igual que un ferry que transporta personas de un lado a otro del río, queríamos desarrollar un mechanism que permitiera que las.” nanopartículas atravesaran vasos sanguinges intactos», explained Li.

Cuando se inyectaron en ratones, alrededor del del 10% de las nanopartículas llegaron al tumor, una mejora significativa con respecto la majoja de las otras plataformas de nanoportadores.

Los researchers probaron su plataforma en modelos de ratones con cáncer de colon y de pancreas. Los animals treated with nanoparticles that contained both FuOXP and siRNA had better tumoral microenvironments with more T cells that combat cancer and less immunosuppressive regulatory T cells than animals that received placebo or a dose of FuOXP.

As a result, the rats received the siRNA-FuOXP nanoparticles it shows a drastic decrease in the size of the tumor en comprásiona con los animales que cierpeño solo una therapy.

According to Li, the study also pointed to the potential of combining FuOXP siRNA nanoparticles with another type of immunotherapy called checkpoint inhibitors. The immune checkpoints, like PD-1, act as a brake on the immune system, but the checkpoint inhibitors function before releasing the brakes and helping the immune cells fight cancer.

The researchers found that FuOXP nanoparticles with or without siRNA increased the expression of PD-1. But when they added a PD-1 inhibitor drug, the combined therapy showed drastic improvements in tumor growth and survival in rats.

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