Construction of magnetic-carbon-quantum-dots-probe-labeled apoferritin nanocages for bioimaging and targeted therapy Hanchun Yao,1,2 Li Su,1 Man Zeng,1 Li Cao,1 Weiwei Zhao,1 Chengqun Chen,3 Bin Du,1,2 Jie Zhou1,2 1School of Pharmaceutical Sciences, Zhengzhou University, 2Collaborative Innovation Center of Drug Research and Safety Evaluation, Henan Province, 3Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Carbon dots (CDs) are one of the most highlighted carbon-based materials for biological applications, such as optical imaging nanoprobes, which are used for labeling cells in cancer treatment mainly due to their biocompatibility and unique optical properties. In this study, gadolinium (Gd)-complex-containing CDs were obtained through a one-step microwave method to develop multimodal nanoprobes integrating the advantages of optical and magnetic imaging. The obtained Gd-CDs exhibited highly fluorescent properties with excellent water solubility and biological compatibility. Natural apoferritin (AFn) nanocages, an excellent drug delivery carrier, are hollow in structure, with their pH-dependent, unfolding–refolding process at pH 2.0 and 7.4. The chemotherapeutic drug doxorubicin (DOX) can be highly effective and encapsulated into AFn cavity. A widely used tumor-targeting molecule, folic acid (FA), functionalized the surface of AFn to obtain an active tumor targeting effect on MCF-7 cells and malignant tumors in mice models. In this study, an AFn nanocarrier encapsulating high concentration of DOX labeled with magnetic and fluorescent Gd-CDs probe was developed. Gd-CDs exhibited a unique green photoluminescence and almost no toxicity compared with free GdCl3. Furthermore, Gd-doped CDs significantly increased the circulation time and decreased the toxicity of Gd3+ in in vitro and in vivo magnetic resonance imaging, which demonstrated that the AFn nanocages labeled with Gd-CD compounds could serve as an excellent T1 contrast agent for magnetic resonance imaging. The self-assembling multifunctional Gd-CDs/AFn (DOX)/FA nanoparticles have a great potential for cancer theranostic applications. Keywords: Gd-CDs, fluorescence, magnetic, apoferritin nanocages, imaging

Image-guided cancer nanotheranostics with a simple nano-platform are seriously significant for nanomedicine. In this study, a novel design is described to achieve sensitive bio-imaging and effective treatment by utilizing heavy-chain ferritin (HFn) nanocages as a vector coupled with dual-functional carbon dots (CDs) on the surface of ferritin and encapsulating the chemotherapeutic drug doxorubicin (DOX). The CDs obtained herein emit bright fluorescence in the red region, which can be applied to bio-imaging in vivo. More significantly, the CDs can produce reactive oxygen species (ROS) under laser irradiation at 532 nm and cause damage to the DNA in the nucleus. These unique properties enabled CDs to act as a theranostic agent. Owing to the self-targeting ability of HFn, the final nanoparticles can internalize into cancer cells more efficiently. The nanoparticles can translocate into the nucleus after DNA damage resulting from the partial release of DOX into the cytoplasm, thereby increasing the nuclear delivery of the drug. The results of this study indicate that the multifunctional HFn(DOX)/CD nanoparticles have potential as a clinically available cancer theranostic agent to deliver diagnostic agents and therapeutic drugs into the cancer cells and thus provide a noninvasive, highly sensitive imaging approach and guidance to the chemo-photodynamic therapy simultaneously.