A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis

Abstract To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19 F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H 6 ) to form H 6 -PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H 6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19 F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.