1.Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, State Key Laboratory for Manufacturing Systems Engineering, Instrument Analysis Center, Xi’an Jiaotong University, Xi’an, 710000, China ;2.School of Materials Science and Engineering, National Institute for Advanced Materials, Center for Rare Earth and Inorganic Functional Materials, Nankai University, Tianjin, 300350, China ;3.Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710000, China ;4.Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, New York, 11973, USA ;
Abstract:
Developing a reliable system to efficiently and safely deliver peptide drugs into tumor tissues still remains a great challenge since the instability of peptide drugs and low ability to traverse the cell membrane. Herein, we constructed a multifunctional nanoplatform based on porous europium/gadolinium (Eu/Gd)-doped NaLa(MoO4)2 nanoparticles (NLM NPs) to deliver antitumor peptide of B-cell lymphoma/leukemia-2-like protein 11 (BIM) for cancer therapy. The porous NLM NPs exhibited inherent photoluminescent, magnetic and X-ray absorbable properties, which enable them for triple-modal bioimaging, including fluorescence, magnetic resonance imaging (MRI) and computed tomography (CT). This triple-modal bioimaging can contribute to monitoring NLM NPs biodistribution and guiding therapy in vitro and in vivo. Furthermore, the NLM NPs showed negligible cytotoxicity in vitro and tissue toxicity in vivo. Importantly, NLM NPs could load the antitumor peptide of BIM and efficiently improve the resistance of peptide drugs to proteolysis. The BIM peptide was efficiently delivered into the tumor cells by NLM NPs, which can inhibit the growth and promote the apoptosis of cancer cells in vitro, significantly inhibit the tumor growth in vivo. Notably, NLM-BIM theranostic nanoplatform exhibits low systemic toxicity and fewer side effects in vivo. The NLM NPs can serve as a promising multifunctional peptide delivery nanoplatform for multi-modal bioimaging and cancer therapy.