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Enzyme-Controlled Intracellular Self-Assembly of (18)F Nanoparticles for Enhanced MicroPET Imaging of Tumor.

Liu Y, Miao Q, Zou P, Liu L, Wang X, An L, Zhang X, Qian X, Luo S, Liang G - Theranostics (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

HPLC traces of SFB (black, absorbance at 254 nm), 1-Cold (red, absorbance at 320 nm), 18F-SFB (green, radiochromatograph), 1 (blue, radiochromatograph), and reaction mixture of 1 (cyan, radiochromatograph), respectively.
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Figure 4: HPLC traces of SFB (black, absorbance at 254 nm), 1-Cold (red, absorbance at 320 nm), 18F-SFB (green, radiochromatograph), 1 (blue, radiochromatograph), and reaction mixture of 1 (cyan, radiochromatograph), respectively.

Mentions: To ensure a successful radio-synthesis of 1, we used a radio-HPLC equipped with a UV-vis detector and a γ-counter to monitor the reaction. In detail, 18F-SFB was synthesized according to the literature and purified with a C18 Sep-Pak cartridge. Compared with SFB which has a retention time of 14.1 min on the HPLC chromatograph, purified 18F-SFB has a retention time of 14.2 min and radiochemical purity more than 90% (Figure 4). After that, 18F-SFB (20 µL, 5 mCi) was added into the solution of 2 (100 µg, 90 nmol) dissolved in 150 µL phosphate buffered saline (PBS) at pH 7.2, heated at 50 °C for 0.5 h. Then the reaction mixture was injected into the radio-HPLC for purification and analysis. As shown in Figure 4, the flatheaded HPLC peak at 15.9 min on the radio-HPLC trace, which has a same retention time to that of 1-Cold, was collected and purified as 1 with 50% radiochemical yield (RCY) (decay-corrected to the end of synthesis, EOS) and specific radioactivity of 0.6 ± 0.4 Ci µmol-1 (EOS). The amount of unreacted 18F-SFB in the mixture, which has a retention time of 14.4 min, was very tiny. Stability study indicated that 1 was stable in fetal bovine serum at 37 °C up to 5 h (97.7%) (Supplementary Material: Figure S15).


Enzyme-Controlled Intracellular Self-Assembly of (18)F Nanoparticles for Enhanced MicroPET Imaging of Tumor.

Liu Y, Miao Q, Zou P, Liu L, Wang X, An L, Zhang X, Qian X, Luo S, Liang G - Theranostics (2015)

HPLC traces of SFB (black, absorbance at 254 nm), 1-Cold (red, absorbance at 320 nm), 18F-SFB (green, radiochromatograph), 1 (blue, radiochromatograph), and reaction mixture of 1 (cyan, radiochromatograph), respectively.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508496&req=5

Figure 4: HPLC traces of SFB (black, absorbance at 254 nm), 1-Cold (red, absorbance at 320 nm), 18F-SFB (green, radiochromatograph), 1 (blue, radiochromatograph), and reaction mixture of 1 (cyan, radiochromatograph), respectively.
Mentions: To ensure a successful radio-synthesis of 1, we used a radio-HPLC equipped with a UV-vis detector and a γ-counter to monitor the reaction. In detail, 18F-SFB was synthesized according to the literature and purified with a C18 Sep-Pak cartridge. Compared with SFB which has a retention time of 14.1 min on the HPLC chromatograph, purified 18F-SFB has a retention time of 14.2 min and radiochemical purity more than 90% (Figure 4). After that, 18F-SFB (20 µL, 5 mCi) was added into the solution of 2 (100 µg, 90 nmol) dissolved in 150 µL phosphate buffered saline (PBS) at pH 7.2, heated at 50 °C for 0.5 h. Then the reaction mixture was injected into the radio-HPLC for purification and analysis. As shown in Figure 4, the flatheaded HPLC peak at 15.9 min on the radio-HPLC trace, which has a same retention time to that of 1-Cold, was collected and purified as 1 with 50% radiochemical yield (RCY) (decay-corrected to the end of synthesis, EOS) and specific radioactivity of 0.6 ± 0.4 Ci µmol-1 (EOS). The amount of unreacted 18F-SFB in the mixture, which has a retention time of 14.4 min, was very tiny. Stability study indicated that 1 was stable in fetal bovine serum at 37 °C up to 5 h (97.7%) (Supplementary Material: Figure S15).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus