From Biology to Biology: Hematoporphyrin-melanin Nanoconjugates with Synergistic Sonodynamic-photothermal Effects on Malignant Tumors

Abstract Compared to the synthetic nanomaterials, the ones modified from biology and capable of multimodal imaging and therapeutic functions have received increasingly interest for tumor theranostics due to their intrinsic biocompatibility and biodegradability. In this work, we firstly prepared the hematoporphyrin-melanin nanoconjugates (HMNCs) whose hematoporphyrin part was originated from the endogenous hemoglobin and melanin part was extracted from the cuttlefish ink. In the case of HMNCs, the hematoporphyrin part could be excited by ultrasound to produce cytotoxici singlet oxygen for sonodynamic therapy (SDT), while the melanin part with strong near-infrared absorbance possessed rapid and efficient photothermal conversion for photothermal therapy (PTT). The in vitro cell experiments confirmed the high biocompatibility of HMNCs, and the combined SDT-PTT achieved much high therapeutical efficacy towards cancer cells in comparison to SDT or PTT alone. Furthermore, in vivo administration of HMNCs at 40 mg kg-1 brings no noticeable side effect for mice blood and major organs, showing their high in vivo biosafety. The HMNCs could accumulate in tumor area after intravenously injection so that it provided high contrast for tumor photoacoustic and thermal imaging, and thereafter the tumor growth was highly inhibited through synergistic SDT-PTT in comparison to SDT or PTT alone. Therefore, the HMNCs modified from biology can be served as multifunctional nanoagents for tumor theranostic, and it would inspire to develop novel agents modified from biology and then utilize them for biology.