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. Her...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.展开更多
基金National Key R&D Program of China (No. 2017YFA0208000)the China National Funds for Excellent Young Scientists (No. 21522106)+3 种基金Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of Stomatology, Xian Jiaotong University (No. 2018LHM-KFKT004)National Natural Science Foundation of China (Nos. 51502237, 51872224, and U1501245)We also appreciate Dr. Dong Su from the Center for Functional Nanomaterials at Brookhaven National Laboratory for his kind help in Electron Microscopy (EM) work.
文摘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.
