Abstract
Graphical abstract
Keywords
1. Introduction
2. Experiment section
3. Results and discussion
4. Conclusions
Declaration of Competing Interest
Acknowledgements
Appendix A. Supplementary data
References
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 cytotoxic 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 effects for mice blood and major organs, showing their high in vivo biosafety. The HMNCs could accumulate in tumor area after intravenously injection so that they 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.
1. Introduction
Malignant tumors with rapid and uncontrolled growth brings a heavy burden on physical, mental and economic state of patients. To treat these tumors, apart from the clinically used therapeutical approaches, several emerging treatment modalities have been explored by taking advantage of the advanced nanotechnology, such as photosensitizer-based photodynamic therapy [1,2], nutrition-depletioninduced starvation therapy [3,4], nanocarriers-based chemotherapy [5–7], and sonosensitizer-driven sonodynamic therapy (SDT) [8–11] et al. Among these therapies, SDT stands out because it utilizes unharmful ultrasound (US) as the energy source which possesses higher tissue-penetration depth than photodynamic therapy, so that sonosensitizers accumulated within tumor can be efficiently in-situ excited to produce cytotoxic radical oxygen species (ROS) to destroy cancer cells, while bringing a low side-effect for the normal tissue [9]. Currently, a number of sonosensitizers have been prepared which can be basically categorized into inorganic semiconductors (such as TiO2 nanoparticles [12] and its nanocomposites [13,14]) and organic molecules including hypocrellins [15], protoporphyrin [16], hematoporphyrin [17–19] and et al. However, the therapeutical efficacy of tumor SDT is rather limited by the low oxygen level in solid tumors as well as the short life time (~200 ns) and diffusion distance (<20 nm) of ROS [2]. Therefore, it is urgent to improve the therapeutical efficacy of SDT.