Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging

Phototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Forster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water-soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal-to-liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging. A nanostructured supramolecular phototherapeutic agent (PcDA) was developed based on the Forster resonance energy transfer mechanism. PcDA can enable the visualization of a tumor with a photoacoustic signal-to-liver ratio as high as 11.9, and 95% of tumor growth is suppressed through photodynamic and photothermal synergistic therapy at a PcDA dose of 0.8 nmol g-1 and a light dose of 300 J cm-2. image