Pincer‐Type Pt(II)‐NHC Antibody‐Drug Conjugate for HER‐2‐Targeted Chemoimmunotherapy

The antibody-drug conjugate Trastuzumab-Pt1 has demonstrated successful development as a targeted therapeutic strategy for human epidermal growth factor receptor (HER-2) high-expression tumors. This innovative approach enables the efficient delivery of the cytotoxic payload Pt-1 to mitochondria, thereby synergistically inducing necroptosis and immunogenic cell death. By combining Trastuzumab's HER2-targeting ability with Pt-1’s dual cell death effect, Trastuzumab-Pt1 exhibits enhanced therapeutic efficacy.

Abstract

Platinum-based chemotherapy drugs play an indispensable role in clinical cancer treatment, but exhibit considerable side effects due to their non-specific mechanism of killing cancer cells and normal cells. In this regard, the use of antibodies conjugated to anti-cancer platinum complexes will enable better differentiation of cancer cells from normal cells. Here, six pincer-platinum(II) NHC (N-heterocyclic carbene) complexes are reported, one of which has an amino group on the N-alkyl group of the NHC ligand. This platinum(II) complex is used as the payload for platinum(II)-based antibody-drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER-2). Notably, this ADC can specifically bind to the HER-2 antigen, distinguish target cells from non-target cells, and exhibit good anti-tumor activity in vitro and in vivo.