NIR laser-activated phthalocyanine loaded lipid nanoparticles targeting M2 macrophage for improved photoacoustic imaging-guided photothermal therapy

The development of novel phototheranostic agents with significant potential in bioimaging-guided therapy is highly desirable for precise tumor therapy. Herein, NIR laser-activated ruthenium phthalocyanine (PcRu) loaded sub-30 nm targeting lipid nanoparticles (alpha-PcRu-NPs) were fabricated for photoacoustic imaging (PAI)-guided photothermal therapy (PTT). Due to the formation of J-type aggregation of PcRu in the core of the nanostructure, the alpha-PcRu-NPs exhibited high stability, efficient NIR absorption, reduced singlet oxygen generation, high photothermal activity, and intense photoacoustic signal. With the M2 macrophage target peptide (M2pep) modification and small size of alpha-PcRu-NPs, in vivo evaluations reveal that alpha-PcRu-NPs can specifically target and deeply penetrate the tumor foci. Under a high contrast PAI guidance with alpha-PcRu-NPs (744 nm, 0.35 mu W), it also realizes superior photothermal therapy (PTT) for breast cancer under 670 nm laser irradiation (0.5 W/cm(2)). The prominent therapeutic efficacy of alpha-PcRu-NP-based PTT not only directly kills tumor cells, but also enhances the immune response by promoting dendritic cell maturation and increasing cytotoxic T cell infiltration. Thus, this work broadens the applications of phthalocyanine derivatives as phototheranostics in the PAI-guided PTT field.