Siguiente generación de bioensamblajes de proteína-corrol para un tratamiento tumoral eficaz en un modelo de cáncer...

Assemblies that combine chemotherapeutics with tumor-targeting proteins are promising agents for treating resistant cancers but require full biochemical characterization before therapeutic deployment. We developed and optimized a HER3 targeting capsomere, HPK2.0, which forms stable nanoscale assemblies with cytotoxic corroles via electrostatic neutralization and shape complementarity. These nanocomplexes exhibit durable serum stability, HER3 dependent tumor invasion, and efficient endosomal escape, resulting in potent and selective cytotoxicity in triple negative breast cancer (TNBC) cells. In an orthotopic metastatic TNBC model, systemic treatment with HPK2.0 corrole assemblies achieved 67 to 83% tumor regression, near-complete suppression of spontaneous lung metastasis, and a ~2 fold improvement in survival relative to mock treatment, with minimal off-target toxicity. By integrating tumor specificity with therapeutic potency, this next-generation protein corrole platform establishes a clinically scalable strategy for treating metastatic HER3 positive TNBC.