A nanoparticle opens a new way against cancer

A team led by Ramón Martínez Máñez, researcher of the Polytechnic University of Valencia (UPV)has developed a pioneering nanoparticle capable of reestablishing communication between tumor cells and immune cells. This communication, which is usually lost in tumors due to immune evasion mechanisms, is key for the immune system to detect and eliminate cancer cells. The work opens a new therapeutic avenue in the field of nanoimmunotherapy.

The innovative nanoparticle is inspired by bispecific antibodies (BiTEs), a clinically approved tool for treat hematological tumors, but it has drawbacks: a complex production process, a short lifespan in the body, limited effectiveness in tumors solids and adverse side effects, the university center has indicated in a statement.

The Janus-type nanoparticles developed by the research group overcome these drawbacks, as they are easy to produce and adapt to different types of cancer and have a longer lifespan in the body than BiTEs, which allows them to accumulate more effectively in tumors, with a lower risk of side effects.

Metastasis reduction

In in vitro cultures with human melanoma cells and immune cells (lymphocytes), it has been shown that these innovative nanoparticles, called J-pHLIP-PD1, remain exposed on the membrane of tumor cells and show their other side towards lymphocytes.

In this way, the nanoparticle mediates the interaction between lymphocyte and tumor cell and acts as a bridge facilitates the death of the cancer cell. Its therapeutic potential has also been tested in a mouse metastasis model, a difficult-to-treat cancer, with very encouraging results, since the nanoparticles have significantly reduced the formation of metastases in the animals’ lungs.

“This superior efficacy can be attributed to its ability to reestablish communication between the immune system and the tumor, since a significant increase in cytotoxic lymphocytes was observed in the lungs of mice treated with the nanoparticles,” explained the researcher. Ramón Martínez Máñez.

The application of Janus-type nanoparticles in immunotherapy represents a step forward in innovation, since it allows different types of ligands to be precisely targeted to bind cells, something that is not possible with other types of nanoparticles.

“One side specifically recognizes tumor cells – in this study, melanoma – and the other binds to immune cells. In this way, the nanoparticle acts as a bridge between the two, imitating the natural immune synapse and reestablishing communication between the two cell types,” he pointed out. Alba García.

Applications and next steps

According to the research team, although the study has focused on metastatic melanoma, this technology could easily be adapted to other types of solid or hematological tumors.

The team is already working on its validation for the treatment of more complex solid tumors, including breast cancer triple negative, where physical barriers make it difficult for the immune system to access and conventional immunotherapy presents limited results.

“These nanoparticles have greater stability and ability to concentrate in tumor areas and are expected to achieve good results in the most difficult tumors,” they clarified.

In addition, its porous core allows loading drugs and combining different strategies in a single system. The work has been published in the journal Advanced Materials and carried out by the Nanosens group of the IDM of the UPV, which is part of the UPV – CIPF and UPV – IIS La Fe Mixed Units. The members of the research group are also part of the CIBER-BBN.