Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T‐DM1) Through Nano‐Delivery System in Breast Cancer Therapy

Abstract Trastuzumab emtansine (T‐DM1), an antibody‐drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T‐DM1 demonstrates superior efficacy and tolerability, T‐DM1‐induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles as a delivery vehicle to conjugate T‐DM1, aiming to alleviate T‐DM1‐induced thrombocytopenia. The T‐DM1‐conjugated PLGA nanoparticles (NPs‐T‐DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs‐T‐DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T‐DM1‐induced thrombocytopenia, and remarkably improves the safety of antibody‐conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T‐DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2‐positive breast cancer patients.