Polynorepinephrine Nanoparticles: A Novel Photothermal Nanoagent for Chemo-Photothermal Cancer Therapy

Novel photothermal nanoagents (PTNAs) with excellent photothermal performance, smart-responsive property, and biocompatibility are in urgent need for precise chemo-photothermal cancer therapy. Herein, polynorepinephrine nanoparticles (PNE NPs) with a high photothermal conversion efficiency (η) of 808 nm laser (67%), pH/thermal responsibility, and little to no long-term toxicity were synthesized from an endogenic neurotransmitter norepinephrine. Compared to their analogues, polydopamine NPs, a widely used PTNA, PNE NPs exhibited a higher η value (enhanced 1.63-fold) and better cellular uptake efficiency (enhanced 2.57-fold). After modifying with polyethylene glycol (PEG) and loading with doxorubicin (DOX), PNE-PEG@DOX could realize responsive release of DOX under either a cytolysosome pH microenvironment (pH 5.0) or an 808 nm laser irradiation, resulting in an enhanced chemotherapeutic efficacy of DOX. Besides, in vivo combination therapy leads to nearly complete ablation of tumor tissues, while no significant side effects were found in normal tissues. Hence, this intelligent and biocompatible nanoplatform based on PNE NPs holds great potential in promoting the clinic transformation of precise chemo-photothermal cancer therapy.