The rational design of theranostic nanoparticles exhibiting synergistic turn-on of therapeutic potency and enhanced diagnostic imaging in response to tumor milieu is critical for efficient personalized cancer chemotherapy. We herein fabricate self-reporting theranostic drug nanocarriers based on hyperbranched polyprodrug amphiphiles (hPAs) consisting of hyperbranched cores conjugated with reduction-activatable camptothecin prodrugs and magnetic resonance (MR) imaging contrast agent (Gd complex), and hydrophilic coronas functionalized with guanidine residues. Upon cellular internalization, reductive milieu-actuated release of anticancer drug in the active form, activation of therapeutic efficacy (>70-fold enhancement in cytotoxicity), and turn-on of MR imaging (∼9.6-fold increase in T1 relaxivity) were simultaneously achieved in the simulated cytosol milieu. In addition, guanidine-decorated hPAs exhibited extended blood circulation with a half-life up to ∼9.8 h and excellent tumor cell penetration potency. The hyperbranched chain topology thus provides a novel theranostic polyprodrug platform for synergistic imaging/chemotherapy and enhanced tumor uptake.
Iron (Fe) is an essential micronutrient for plant growth development and plays a key role in regulating numerous cellular processes. In rice, OsHRZ1, an Fe‐binding ubiquitin ligase, is a putative sensor of Fe homeostasis that negatively regulates iron acquisition. Despite its apparent importance, only a single basic‐Helix–Loop–Helix (bHLH) transcription factor, OsPRI1, has been identified as a direct target of OsHRZ1. In this study, we identified and functionally characterized OsPRI2 and OsPRI3, two paralogs of OsPRI1, observing that they directly interact with OsHRZ1. Additional analyses suggested that OsHRZ1 promotes the degradation of OsPRI2 and OsPRI3. The translocation of Fe from roots to shoots was impaired in plants with loss‐of‐function mutations in OsPRI2 or OsPRI3, causing the downregulation of Fe‐deficiency‐responsive genes. In contrast, overexpression of OsPRI2 and OsPRI3 promotes Fe accumulation and activates the expression of Fe‐deficiency‐responsive genes. We also provide evidence that OsPRI2 and OsPRI3 bind to the promoters of OsIRO2 and OsIRO3, two key regulators of Fe homeostasis. Moreover, OsPRI2 and OsPRI3 directly induce expression of the metal‐nicotianamine transporter, OsYSL2, by associating with the promoter in response to Fe deficiency. Our results provide insights into the complex network regulating Fe homeostasis in rice.
The one-step pyrolysis of a zeolite-type metal-organic framework, Co(2-methylimidazole)2 (ZIF-67), produces an N-doped porous carbon incorporating well-dispersed Co/CoO nanoparticles, which exhibit excellent catalytic activity, chemoselectivity and magnetic recyclability for the tandem dehydrogenation of ammonia borane and hydrogenation of nitro compounds at room temperature.
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