Endogenous Albumin-Mediated Disassembly of Phthalocyanine Nanoparticles for Tumor-Selective Imaging and Sonodynamic Therapy

Albumin, the most abundant plasma protein, is a clinically significant biomarker that has been extensively utilized as an endogenous carrier for drug delivery due to its high binding affinity for hydrophobic ligands and its tendency to accumulate and be metabolized in tumors. Sonodynamic therapy (SDT) combines low-intensity ultrasound with sonosensitizers to produce cytotoxic reactive oxygen species, offering deep tissue penetration and spatiotemporal control that can complement or even surpass traditional photodynamic therapies. However, there is a need for straightforward, activatable platforms that link tumor-associated albumin recognition with selective SDT activation. In this study, we engineer an amphiphilic zinc-(II) phthalocyanine derivative that self-assembles into albumin-responsive nanoaggregates (NanoPcS). These aggregates exhibit quenched fluorescence and sonoactivity, which are activated upon binding to albumin and subsequent disassembly. This versatile design allows NanoPcS to serve as both an activatable probe and an effective SDT agent, enabling fluorescence reporting of albumin-rich tumor microenvironments while also generating ultrasound-triggered reactive oxygen species for cancer treatment.