Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy

The study reports a multifunctional nanoplatform based on mesoporous silica coated gold nanorod (AuNR@MSN) to overcome biological barriers associating with nanocarrier for multiple enhanced photodynamic therapy (PDT) and photothermal therapy (PPT). Indocyanine green (ICG) was loaded into AuNR@MSN and end-capped with β-cyclodextrin (β-CD). Then, a peptide RLA ([RLARLAR]2) with plasma membrane permeability and mitochondria-targeting capacity was anchored to AuNR@MSN via host-gust interaction. Subsequently, a charge-reversible polymer was introduced to endow stealth property. When the nanoplatform extravasates to tumor tissue, the weak acidity in tumor microenvironment could induce the dissociation of charge-reversible polymer and re-exposure of RLA peptide. Such a pH-mediated transition could facilitate the targeted accumulation of the nanoplatform in mitochondria. Upon singular 808 nm laser irradiation, the nanoplatform displayed enhanced PDT effect through the generation of reactive oxygen species (ROS) mediated by the local electric field of AuNR, plasmonic photothermal effect, and leakage of endogenous ROS by mitochondrion-targeted PDT. Meanwhile, local hyperthermia was generated by both ICG and AuNR for PPT. The in vitro and in vivo experiments demonstrated that the composite nanoplatform had good antitumor effect with minimal side effect. This work provides new insight into the development of new phototherapeutics for oncotherapy.