Nan Wang,Mingjian Zhu,Yiming Jiang,Daoming Zhang,Jiachen Lin,Jiahe Wu,Nengming Lin,Jianqing Gao
The deficient discrimination of tumor cells, limited accumulation of therapeutic agents in tumor foci, and undesirable tumor metastasis result in compromised therapeutic efficacy in antitumor therapy. Neutrophils, the most abundant circulating leukocytes, are key players in tumor progression and have a high affinity to tumors. Herein, a biomimetic tumor discrimination nanodevice (NL-FSB) is developed by harboring a pH-sensitive Fenton agent (FSB) in an activated neutrophil membrane-incorporated liposome for tumor-specific ablation. Inheriting the biointerfacing properties of neutrophils, NL-FSB is endowed with high affinity to tumors. On one hand, NL-FSB can be recruited to acidic tumor sites mediated by chemotaxis attraction and selectively generate reactive oxygen species via amplified Fenton chemical reaction for specific tumor eradication. On the other hand, the biomimetic NL-FSB can also target and bind tumor vascular endothelium or circulating tumor cells (CTCs) in circulation, executing pseudo escort to perturb CTC-neutrophil cluster formation and tumor metastasis cascade. Unprecedentedly, the neutrophil-mediated nanoagent can effectively inhibit the already-formed tumor and prevent tumor metastasis with high specificity. Our study represents a promising yet simple strategy for tumor-specific killing and metastasis cascade blockage via a nanobioengineering functionalization strategy.
The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG 2K -FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG 2K ) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG 2K -FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG 2K -FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.
X X Cui,Q Fan,S J Shi,W H Wen,D F Chen,H T Guo,Y T Xu,F Gao,R Z Nie,Harold D Ford,Gordon H Tang,C Q Hou,B Peng
Fluorescence imaging signal is severely limited by the quantum efficiency and emission wavelength. To overcome these challenges, novel NIR-emitting K5NdLi2F10 nanoparticles under NIR excitation was introduced as fluorescence imaging probe for the first time. The photostability of K5NdLi2F10 nanoparticles in the water, phosphate buffer saline, fetal bovine serum and living mice was investigated. The fluorescence signal was detected with depths of 3.5 and 2.0 cm in phantom and pork tissue, respectively. Fluorescence spectrum with a significant signal-to-background ratio of 10:1 was captured in living mice. Moreover, clear NIR images were virtualized for the living mice after intravenous injection. The imaging ability of nanoparticles in tumor-beard mice were evaluated, the enrichment of K5NdLi2F10 nanoparticles in tumor site due to the enhanced permeability and retention effect was confirmed. The systematic studies of toxicity, bio-distribution and in-vivo dynamic imaging suggest that these materials give high biocompatibility and low toxicity. These NIR-emitting nanoparticles with high quantum efficiency, high penetration and low toxicity might facilitate tumor identification in deep tissues more sensitively.
危险品化学品经营许可证（带存储）