Dual antibody-aided mesoporous nanoreactor for H2O2 self-supplying chemodynamic therapy and checkpoint blockade immunotherapy in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) represents a formidable challenge due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, rendering it unresponsive to conventional hormonal and targeted therapies. This study introduces the development of mesoporous nanoreactors (NRs), specifically mPDA@CuO₂ NRs, as acid-triggered agents capable of self-supplying H₂O₂ for chemodynamic therapy (CDT). To enhance therapeutic efficacy, these NRs were further modified with immune checkpoint antagonists, specifically anti-PD-L1 and anti-CD24 antibodies, resulting in the formation of dual antibody-aided mesoporous nanoreactors (dAb_PD-L1/CD24-mPDA@CuO₂ NRs). These NRs were designed to combine CDT and checkpoint blockade immunotherapy (CBIT) for precise targeting of 4T1 TNBC cells. Remarkably, dAb_PD-L1/CD24-mPDA@CuO₂ NRs exhibited tumor-targeted CDT triggered by H₂O₂ and successfully activated immune cells including T cells and macrophages. This integrated approach led to a remarkable inhibition of tumor growth by leveraging the collaborative effects of the therapies. The findings of this study introduce a novel and promising strategy for the integrative and collaborative treatment of refractory cancers, providing valuable insights into addressing the challenges posed by aggressive breast cancer, particularly TNBC.

Keywords: Checkpoint blockade immunotherapy; Chemodynamic therapy (CDT); Collaborative treatment; Mesoporous nanoreactors; Triple-negative Breast cancer (TNBC).