New smart nanoparticles created capable of eliminating tumor cells and stopping melanoma

A team from the Polytechnic University of Valencia (UPV), belonging to the Interuniversity Institute for Molecular Recognition and Technological Development (IDM), and the CIBER for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), the LA Fe Health Research Institute (IIS La Fe), together with the UPV-Prince Felipe Research Centre (CIPF) Joint Unit, has developed innovative nanoparticles in the preclinical phase that are capable of locating and eliminating senescent tumor cells , which are responsible for cancer relapses. The work has been published in the journal Biomaterials .

Senescent cells are those that stop dividing, but do not die. In cases of cancer, although they initially slow tumor progression, over time they can generate an inflammatory tumor environment and promote disease recurrence. So far, drugs known as senolytics have shown "some" efficacy against these senescent cancer cells, "but their severe side effects have limited their clinical application ," the academic institution explained in a statement.

A two-phase treatment

In their work, the team from the UPV, CIBER-BBN, IIS La Fe, and CIPF has designed mesoporous silica nanoparticles loaded with the drug navitoclax and coated with an antibody that recognizes a protein overexpressed on the surface of senescent cells: DPP4. Thus, the nanoparticles act as a 'Trojan horse': they travel through the body without releasing the drug and only do so when they detect senescent cells in the tumor, achieving a precise elimination of these harmful cells.

In preclinical models of human melanoma, this strategy by the UPV-led team has significantly reduced tumor size. "We demonstrated that it is possible to target nanoparticles against the DPP4 protein to eliminate senescent cancer cells. This opens the door to new, much more selective therapies with fewer side effects," explained Ramón Martínez-Máñez, director of the UPV's IDM Institute.

The treatment combines two steps, what researchers call a "one-two punch" strategy: first, palbociclib is administered, a drug already in clinical use that induces senescence in tumor cells. Then, the nanoparticles locate and destroy these cells , releasing navitoclax inside them. "This way, we not only slow tumor growth, but we also prevent these persistent cells from causing relapses," noted Alba García-Fernández, from CIBER-BBN and the IDM-UPV.

A strategy against the diseases of aging

The main novelty of the Valencian researchers' study is that they have identified that the DPP4 protein is highly expressed in senescent melanoma tumor cells , and they have designed one of the few nanoparticles that specifically target these cells through this surface marker. "This discovery allows us to design more precise systems that use DPP4 as a target, opening up new avenues for cancer therapies," stated Alba García-Fernández.

In addition to melanoma, the UPV team points out that this strategy could be applied to other types of cancer and also to diseases associated with aging where the accumulation of senescent cells plays an important role.

"It's a further step toward the development of personalized and safer nanomedicines . Our work demonstrates that we can design intelligent systems that recognize specific harmful cells and act preferentially on them," added Ramón Martínez Máñez.

References

Blanca Escriche-Navarro, Eva Garrido, Andrea Escudero, Isabel Montoya-Méndez, Félix Sancenón, Alba García-Fernández, Ramón Martínez-Máñez. Targeting the senescent surfaceome through DPP4 antibody-functionalized nanoparticles. An application to cancer therapy. Biomaterials (2025). DOI: 10.1016/j.biomaterials.2025.123461