Specific photothermal therapy to the tumors with high EphB4 receptor expression.

Photothermal therapy (PTT) employs photo-absorbing agents to generate heat from optical energy, leading to the 'burning' of tumor cells. Real-time imaging of in vivo distribution of photothermal agents and monitoring of post-treatment therapeutic outcomes are very important to design and optimize personalized PTT treatment. In this work, we used chitosan-stearic acid copolymer (CSO-SA) to encapsulate hollow gold nanospheres (HAuNS) and near-infrared (NIR) fluorescent tracer, DiR. Then, the surface of nanoparticles was further conjugated with a peptide (TNYL), which facilitates EphB4-positive tumor targeting delivery. Using a paired tumor mode in vivo and a double tumor-cell co-culture strategy in vitro, we demonstrated the feasibility of increasing the accumulation of our nanoparticles (DiR loaded and TNYL-CSO-SA coated HAuNS (DTCSH)) into EphB4-positive tumors through interaction between TNYL-peptide on the nanoparticles and EpHB4 receptors on tumor cells. When combined with NIR laser irradiation, our nanoparticles induced more EphB4-positive tumor cells death in vitro. We further developed optical imaging to temporally and spatially monitor the biodistribution of DTCSH. Under NIR laser irradiation, PTT exhibited dramatically stronger antitumor effect against EphB4-positive tumors than EphB4-negative tumors. This was attributed to enhanced accumulation of our nanoparticles in EphB4-positive tumors.