Enzyme-Controlled Intracellular Self-Assembly of ¹⁸F 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.

Increasing Photothermal Efficacy by Simultaneous Intra‐ and Intermolecular Fluorescence Quenching

“…We used the fluorescence imaging of cancer cells to compare the intracellular fluorescence quenching effects among the probes of 1 , 1‐Fmoc , and Cypate. To minimize the interference from intracellular Cys with the CBT‐Cys condensation of 1 or 1‐Fmoc , we used 50 × 10 −6 m Biotin‐Cystamine‐Cys(Fmoc)‐Lys‐CBT ( G , Section S2.1 in the Supporting Information) to coincubate with 1 or 1‐Fmoc throughout the cell experiments . Alamar Blue assay indicated that, even at a high concentration of 400 × 10 −6 m , G did not induce cytotoxicity towards biotin receptor‐overexpressing HeLa cells which were incubated with G for 1 h, washed, and incubated for another 24 h (Figure S15a, Supporting Information).…”

Intracellular Self‐Assembly of Nanoprobes for Molecular Imaging

“…Compared with that of a positive control probe, PET image of the drug‐treated tumor in mouse injected with [ 18 F]C‐SNAT showed obviously enhanced contrast in in vivo. Inspired by this work, Liang and co‐workers reported a “smart” radioactive probe Acetyl‐Arg‐Val‐Arg‐Arg‐Cys(StBu)‐Lys( 18 F‐FB)‐CBT (i.e., 9 in Figure 7 a) that, once co‐injected with its cold analog (i.e., 9‐Cold ), underwent furin‐controlled condensation and self‐assembly of radioactive nanoparticles for enhanced micro‐PET imaging of tumors in nude mice . The underlying reason for this co‐injection strategy lies in the very low chemical concentration (7.1 pmol kg −1 for PET imaging in this work) of the radioactive probe 9 for PET imaging.…”

“…Tumors are indicated by white arrows. Reproduced with permission . Copyright 2015, Ivyspring International Publisher.…”

A protease‐responsive fluorescent probe for sensitive imaging of legumain activity in living tumor cells

“…Recently, magnetic resonance imaging (Chen et al., ; Yuan et al., ), positron emission tomography (Liu et al., ), and fluorescence imaging (Li et al., ) techniques have been developed to directly detect the tumor‐related protease in some studies. In particular, fluorescent probes have attracted much attention due to their advantages of real‐time imaging and high spatial resolution.…”