Senescence-modulating nanoparticles SELECT the right senescent cells to treat fibrosis and cancer.

P-selectin–directed nanoparticles (SMNPs) deliver senotherapies to pathogenic P-selectin+ senescent macrophages in fibrotic mouse lung and liver, resolving fibrosis and restoring organ function.

• Why it matters: Senescence can promote or restrain fibrosis and cancer depending on senescent cell type and its secretory phenotype, yet existing senotherapies lack cell-specific targeting and show limiting toxicities.
• What they did: Hinterleitner and colleagues engineered SMNPs to target P-selectin+ senescent macrophages in fibrotic tissues while avoiding uptake by beneficial senescent endothelial cells, then tested effects in mice and tumor models.
• The result: In mice, SMNP targeting minimized senotherapeutic toxicity and, in tumor models, overcame fibrosis-mediated immune exclusion and sensitized liver and lung cancers to T cell–directed immunotherapy.

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