title: Enzyme-Controlled Intracellular Self-Assembly of (18)F Nanoparticles for Enhanced MicroPET Imaging of Tumor.
abstract: Herein, we report the development of a new "smart" radioactive probe (i.e., 1) which can undergo furin-controlled condensation and self-assembly of radioactive nanoparticles (i.e., 1-NPs) in tumor cells and its application for enhanced microPET imaging of tumors in nude mice co-injected with its cold analog (i.e., 1-Cold). Furin-controlled condensation of 1-Cold and self-assembly of its nanoparticles (i.e., 1-Cold-NPs) in vitro were validated and characterized with HPLC, mass spectra, SEM, and TEM analyses. Cell uptake studies showed that both 1 and 1-Cold have good cell permeability. TEM images of 1-Cold-treated MDA-MB-468 cells directly uncovered that the intracellular 1-Cold-NPs were at/near the location of furin (i.e., Golgi bodies). MTT results indicated that 50 µM 1-Cold did not impose cytotoxicity to MDA-MB-468 cells up to 12 hours. MicroPET imaging of MDA-MB-468 tumor-bearing mice indicated that mice co-injected with 1 and 1-Cold showed higher uptake and longer attenuation of the radioactivity in tumors than those mice only injected with same dosage of 1. Tumor uptake ratios of 1 between these two groups of mice reached the maximum of 8.2 folds at 240 min post injection. Biodistribution study indicated that the uptake ratios of 1 in kidneys between these two groups continuously increased and reached 81.9 folds at 240 min post injection, suggesting the formation of radioactive NPs (i.e., 1-NPs) in MDA-MB-468 tumors of mice co-injected with 1 and 1-Cold. And the nanoparticles were slowly digested and secreted from the tumors, accumulating in the kidneys. Our ''smart'' probe (i.e., 1), together with the strategy of co-injection, might help researchers trace the biomarkers of interest within a longer time window.
authors.affiliation: 1. School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China ; 3. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Miao
authors.affiliation: 3. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zou
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Liu
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Linna
authors.initials: L
authors.lastname: An
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 4. College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Qian
authors.affiliation: 1. School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China ; 3. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
authors.forename: Shineng
authors.initials: S
authors.lastname: Luo
authors.affiliation: 2. CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Gaolin
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D045683:Furin / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000295:instrumentation
chemical_list: D005462:Fluorine Radioisotopes; D010455:Peptides; D045683:Furin
keywords: co-injection.; furin; nanoparticles; self-assembly