Turn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood–brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins.

Hydrogen sulfide (H2S) is considered as a novel second-messenger molecule associated with the modulation of various physiological and pathological processes. In the field of antitumor research, endogenous H2S induces angiogenesis, accelerates the cell cycle and inhibits apoptosis, which results in promoting oncogenesis eventually. Interestingly, high concentrations of exogenous H2S liberated from donors suppress the growth of various tumors via inducing cellular acidification and modulating several signaling pathways involved in cell cycle regulation, proliferation, apoptosis and metastasis. The selective release of certain concentrations of H2S from H2S donors in the target has been considered as an alternative tumor therapy strategy. Triple-negative breast cancer (TNBC), an aggressive subtype with less than one year median survival time, is known to account for approximately 15-20% of all breast cancers. Due to the lack of approved targeted therapy, the clinical treatment of TNBC is still hindered by metastasis as well as recurrence. Significant efforts have been spent on developing novel treatments of TNBC, and remarkable progress in the control of TNBC by H2S donors and their derivatives have been made in recent years. This review summarizes various pathways involved in antitumor and anti-metastasis effects of H2S donors and their derivatives on TNBC, which provides novel insights for TNBC treatment.

Differentiating amyloid beta (Aβ) subspecies Aβ40 and Aβ42 has long been considered an impossible mission with small-molecule probes. In this report, based on recently published structures of Aβ fibrils, we designed iminocoumarin–thiazole (ICT) fluorescence probes to differentiate Aβ40 and Aβ42, among which Aβ42 has much higher neurotoxicity. We demonstrated that ICTAD-1 robustly responds to Aβ fibrils, evidenced by turn-on fluorescence intensity and red-shifting of emission peaks. Remarkably, ICTAD-1 showed different spectra towards Aβ40 and Aβ42 fibrils. In vitro results demonstrated that ICTAD-1 could be used to differentiate Aβ40/42 in solutions. Moreover, our data revealed that ICTAD-1 could be used to separate Aβ40/42 components in plaques of AD mouse brain slides. In addition, two-photon imaging suggested that ICTAD-1 was able to cross the BBB and label plaques in vivo. Interestingly, we observed that ICTAD-1 was specific toward plaques, but not cerebral amyloid angiopathy (CAA) on brain blood vessels. Given Aβ40 and Aβ42 species have significant differences of neurotoxicity, we believe that ICTAD-1 can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.