Supramolecular self-assembly driven platinum-based small molecule for enhanced sonodynamic-immunotherapy

• PtC forms antiparallel dimers via Pt⋯Pt/π-π stacking for enhancing ROS generation under ultrasound • Ultrasound-activated PtC can induce cancer cells apoptosis and ICD. • PtC can inhibit tumor proliferation and elicit systemic anti-tumor immunity. Addressing the critical bottleneck of low reactive oxygen species (ROS) generation efficiency in sonodynamic therapy (SDT), this study proposes a supramolecular self-assembly enhancement strategy. Using dichloro(1,10-phenanthroline)platinum(II) (PtC) as a model molecule, antiparallel dimers were formed via Pt⋯Pt metallophilic interactions and π-π stacking. This induced H-aggregation, widening the energy gap and achieving aggregation-induced emission (AIE). Upon ultrasound activation, the self-assembled PtC nanoparticles exhibited significantly enhanced capabilities for generating singlet oxygen ( 1 O 2 ) and superoxide anion (•O 2 − ) compared to the conventional sonosensitizer protoporphyrin IX (PpIX). In vitro, they induced mitochondrial damage, DNA fragmentation, and immunogenic cell death (ICD) via ROS burst. In vivo experiments confirmed their efficient accumulation in tumor tissues, which not only directly inhibited tumor proliferation but also activated dendritic cell maturation and T cell infiltration, triggering a systemic immune response. This work not only reveals the regulatory mechanism of electronic structure during the self-assembly of platinum complexes on sonodynamic efficacy but also provides a new design paradigm for developing novel sonosensitizers with both high-efficiency sonosensitization and immunostimulatory functions.