A POSS-Based Metal-Phenolic Network with Coupled Hardness and Softness for Photodynamic-Immunotherapy of Triple-Negative Breast Cancer
Wei Wang, Luanfeng Liao, Yun Huang, Yuqi Zhao, Longtianyang Lei, Zhenghao Tao, Jinyan Zhang, Dongdong Peng, Jieqiong Wang, Cui‐Yun Yu, Hua Wei
Abstract
To overcome the oxidative stress and resistance of cancer stem cells (CSCs) for successful metastatic triple-negative breast cancer (TNBC) treatment, we report polyhedral oligosilsesquioxanes (POSS)-based metal-phenolic networks (MPNs) that integrate hard POSS as a rigid dendritic macromolecular moiety for binding with a photosensitizer (PS), Chlorin e6 (Ce6) to improve the reactive oxygen species (ROS) generation efficiency of photodynamic therapy (PDT), and soft metal ions for dynamic coordination-driven co-self-assembly with POSS and an antiapoptotic protein inhibitor, sabutoclax (Sab) to afford MPN nanoparticles (NPs). The MPN NPs show the most significant inhibitory effect in a 4T1 TNBC proximal/distal tumor model with a tumor growth inhibition (TGI) value of 96.8% and significant distal tumor growth inhibition via simultaneous immunogenic cell death (ICD) induction, tumor-associated macrophages (TAMs) polarization, and CSCs elimination. This study presents a facile approach toward the first POSS-based metal-phenolic network with coupled hardness and softness for highly efficient photodynamic immunotherapy of TNBC.