Targeted polydopamine nanoparticles enable photoacoustic imaging guided chemo-photothermal synergistic therapy of tumor.

Near infrared light responsive nanoparticles can transfer the absorbed NIR optical energy into heat, offering a desirable platform for photoacoustic (PA) imaging guided photothermal therapy (PTT) of tumor. However, a key issue in exploiting this platform is to achieve optimal combination of PA imaging and PTT therapy in single nanoparticle. Here, we demonstrate that the biodegradable polydopamine nanoparticles (PDAs) are excellent PA imaging agent and highly efficient for PTT therapy, thus enabling the optimal combination of PA imaging and PTT therapy in single nanoparticle. Upon modification with arginine-glycine-aspartic-cysteine acid (RGDC) peptide, PDA-RGDC can successfully target tumor site. Moreover, PDA-RGDC can load a chemotherapy drug, doxorubicin (DOX), whose release can be triggered by near-infrared (NIR) light and pH dual-stimuli. The in vitro and in vivo experiments show that this platform can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect. Our results offer a way to harness PDA-based theranostic agents to achieve PA imaging-guided cancer therapy. STATEMENT OF SIGNIFICANCE: NIR-light adsorbed nanoparticles combing the advantage of PAI and PTT (TNP-PAI/PTT) are expected to play a significant role in the dawning era of personalized medicine. However, the reported Au-, Ag-, Cu-, Co-, and other metal based, carbon-based TNP-PAI/PTT suffer from complex multicomponent system and poor biocompatibility and biodegradability. To overcome this limitation, biocompatible polydopamine nanoparticles (PDAs), structurally similar to naturally occurring melanin, were designed as both PA imaging contrast agent and a chemo-thermotherapy therapy agent for tumor. RGDC peptide modified PDAs can improve the PA imaging and PTT efficiency and specific targeted deliver doxorubicin (DOX) to perinuclear region of tumor cells. Our finding may help the development of PDA-based nanoplatform for PA imaging-directed synergistic therapy of tumor in clinic.