Targeting TNBC: core-shell polycationic polyurea dendrimers with inherent anticancer activity.

Breast carcinoma (BC) is the most common malignancy in women, with triple-negative breast cancer (TNBC) making up 10-20% of cases. TNBC has limited targeted therapies and poor survival due to late diagnosis and metastasis. Dendrimers are precise nanostructures with a three-dimensional globular architecture designed to target the negatively charged membranes of cancer cells. This study evaluated the anticancer potential of two novel core-shell polycationic polyurea (PURE) dendrimers, PUREG4-OEI48 and PUREG4-OCEI24, targeting BC cell membranes. Both dendrimers selectively interacted with TNBC cells, inducing apoptosis, necroptosis, and ferroptosis. In vivo, they reduced tumor volume in HCC1806 xenografts, with PUREG4-OEI48 showing no toxicity, while PUREG4-OCEI24 induced mild hepatic toxicity. These results suggest PURE dendrimers are promising TNBC treatments, with further modifications needed to enhance efficacy and reduce toxicity.