Nuclear imaging in conjunction with radioactive tracers enables noninvasive measurements of biochemical events in vivo. However, access to tracers remains limited due to the lack of methods for rapid assembly of radiolabeled molecules with the prerequisite biological activity. Herein, we report a one-pot, three-component, copper(II)-mediated reaction of azides, alkynes, and [(125)I]iodide to yield 5-[(125)I]iodo-1,2,3-triazoles. Using a selection of azides and alkynes in a combinatorial approach, we have synthesized a library of structurally diverse (125)I-labeled triazoles functionalized with bioconjugation groups, fluorescent dyes, and biomolecules. Our preliminary biological evaluation suggests that 5-[(125)I]iodo-1,2,3-triazoles are resistant to deiodination in vivo, both as small molecular probes and as antibody conjugates. The ability to incorporate radioactive iodide into triazoles directly from the parent azides and alkynes makes the method broadly applicable and offers the potential to rapidly assemble molecular probes from an array of structurally diverse, and readily available, building blocks.

microRNAs play an important role in the progression of hepatocellular carcinoma (HCC). In this study, we found that miR-582-5p expression was downregulated in hepatoma tissues and HCC cell lines. Upregulation of miR-582-5p reduced colony number, inhibited cellular proliferation, and arrested cell cycle in G0/G1 phase. When miR-582-5p was inhibited, the colony number was increased and cellular proliferation and cell cycle were promoted. Further studies showed that miR-582-5p regulated the progression of HCC through directly inhibiting the expression of CDK1 and AKT3, and indirectly inhibiting the expression of cyclinD1.

Myocardial hypoxia is an attractive target for diagnostic and prognostic imaging, but current approaches are insufficiently sensitive for clinical use. The PET tracer copper(II)-diacetyl-bis (N4-methylthiosemicarbazone) ( 64 Cu-ATSM) has promise, but its selectivity and sensitivity could be improved by structural modification. We have therefore evaluated a range of 64 Cu-ATSM analogs for imaging hypoxic myocardium. Methods: Isolated rat hearts (n 5 5/group) were perfused with normoxic buffer for 30 min and then hypoxic buffer for 45 min within a custom-built triple-g-detector system to quantify radiotracer infusion, hypoxiadependent cardiac uptake, and washout. A 1-MBq bolus of each candidate tracer (and 18 F-fluoromisonidazole for comparative purposes) was injected into the arterial line during normoxia, and during early and late hypoxia, and their hypoxia selectivity and pharmacokinetics were evaluated. The in vivo pharmacokinetics of promising candidates in healthy rats were then assessed by PET imaging and biodistribution. Results: All tested analogs exhibited hypoxia sensitivity within 5 min. Complexes less lipophilic than 64 Cu-ATSM provided significant gains in hypoxic-to-normoxic contrast (14:1 for 64 Cu-2,3-butanedione bis(thiosemicarbazone) (ATS), 17:1 for 64 Cu-2,3-pentanedione bis(thiosemicarbazone) (CTS), 8:1 for 64 Cu-ATSM, P , 0.05). Hypoxic first-pass uptake was 78.2% 6 7.2% for 64 Cu-ATS and 70.7% 6 14.5% for 64 Cu-CTS, compared with 63.9% 6 11.7% for 64 Cu-ATSM. Cardiac retention of 18 F-fluoromisonidazole increased from 0.44% 6 0.17% during normoxia to 2.24% 6 0.08% during hypoxia. In vivo, normoxic cardiac retention of 64 Cu-CTS was significantly lower than that of 64 Cu-ATSM and 64 Cu-ATS (0.13% 6 0.02% vs. 0.25% 6 0.04% and 0.24% 6 0.03% injected dose, P , 0.05), with retention of all 3 tracers falling to less than 0.7% injected dose within 6 min. 64 Cu-CTS also exhibited lower uptake in liver and lung. Conclusion: 64 Cu-ATS and 64 Cu-CTS exhibit better cardiac hypoxia selectivity and imaging characteristics than the current lead hypoxia tracers, 64 Cu-ATSM and 18 F-fluoromisonidazole.

Imaging-guided photothermal therapy (PTT) has promising application for treating tumors. Nevertheless, so far imaging-guided photothermal drug-delivery systems have been developed with limited success for tumor chemo-photothermal therapy. In this study, as the proof-of-concept, a stimuli-responsive tumor-targeting rapamycin/DiR loaded lipid-polyaniline nanoparticle (RDLPNP) for dual-modal imaging-guided enhanced PTT efficacy is reported for the first time. In this system, polyaniline (PANI) with π-π electronic conjugated system and effective photothermal efficiency is chosen as the appropriate model receptor of fluorescence resonance energy transfer (FRET), and loaded cyanine probe (e.g., 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide, DiR) acts as the donor of near-infrared fluorescence (NIRF). In addition, rapamycin (RAPA), which is used as the antiangiogenesis chemotherapeutic drug, can cutdown the tumor vessels and delay tumor growth obviously. After intravenous treatment of RDLPNPs into Hela tumor bearing mice, fluorescent (from DiR) and enhanced photoacoustic (from DLPNPs) signals were found in tumor site over time, which reached to peak at the 6h time point. After irradiating with an NIR laser, a good anti-tumor effect was observed owing to the enhanced photothermal and antiangiogenic effect of RDLPNPs. These results show that the multifunctional nanoparticle can be used as a promising imaging-guided photothermal drug delivery nanoplatform for cancer therapy.

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