Ferroptosis regulates cell death through reactive oxygen species (ROS)‐associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with ...no clear evidence. Herein, we report the first example of an LD/nucleus dual‐targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor–acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual‐targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis‐related diseases.
The first lipid droplet (LD)/nucleus dual‐targeted ratiometric fluorescence probe, CQPP, for monitoring polarity change was developed. CQPP offers ratiometric fluorescence and fluorescence lifetime imaging of LD polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model.
Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis‐inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) ...containing a ferrocene‐modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton‐like reaction, produce hydroxyl radicals, induce lipid peroxidation, down‐regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis‐inducing capabilities for effective cancer immunotherapy.
Ferroptosis‐inducing agents have potential as antitumor candidates. A ferrocene‐modified IrIII complex with Fenton‐like catalytic activity is used to disturb the cellular redox balance, which leads to lipid peroxidation and ferroptosis of cancer cells. Ferroptosis induced by the IrIII complex causes immunogenic cell death (ICD) of cancer cell in vitro, which enhances cancer immune response in vivo.
The nucleus is considered the ideal target for anti‐tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear ...target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear‐targeted material MeTPAE with aggregation‐induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti‐tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
A nuclear‐targeted material MeTPAE with AIE characteristics was developed. MeTPAE can not only interact with HDACs to inhibit cell proliferation, but also damage telomere and nucleic acids precisely through photodynamic treatment. The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent photodynamic therapy (PDT) anti‐tumor activity, which offered new opportunities for the effective treatment of malignant tumors.
A
bstract
We propose a systematic theoretical framework for the topological amplitudes of the heavy meson decays and their SU(
N
) decomposition. In the framework, the topologies are expressed in ...invariant tensors and classified into tree- and penguin-operator-induced diagrams according to which four-quark operators, tree or penguin, being inserted into their effective weak vertexes. The number of possible topologies contributing to one type of decay can be counted by permutations and combinations. The Wigner-Eckhart theorem ensures the topological amplitudes under flavor symmetry are the same for different decay channels. By decomposing the four-quark operators into irreducible representations of SU(
N
) group, one can get the SU(
N
) irreducible amplitudes. Taking the
D → PP
decay (
P
denoting a pseudoscalar meson) with SU(3)
F
symmetry as an example, we present our framework in detail. The linear correlation of topologies in the SU(3)
F
limit is clarified in group theory. It is found there are only nine independent topologies in all tree- and penguin-operator-induced diagrams contributing to the
D → PP
decays in the Standard Model. If a large quark-loop diagram, named
T
LP
, is assumed, the large ∆
A
CP
and the very different
D
0
→ K
+
K
−
and
D
0
→ π
+
π
−
branching fractions can be explained with a normal
U
-spin breaking. Moreover, our framework provides a simple way to analyze the SU(
N
) breaking effects. The linear SU(3)
F
breaking and the high order
U
-spin breaking in charm decays are re-investigated in our framework, which are consistent with literature. Analogous to the degeneracy and splitting of energy levels, we propose the concepts of degeneracy and splitting of topologies to describe the flavor symmetry breaking effects in decay. As applications, we analyze the strange-less
D
decays in SU(3)
F
symmetry breaking into Isospin symmetry and the charm-less
B
decays in SU(4)
F
symmetry breaking into SU(3)
F
symmetry.
Activation of the cyclic GMP‐AMP synthase‐stimulator of the interferon gene (cGAS‐STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way ...to stimulate the anticancer immune responses. Herein, two PtII complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS‐STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS‐STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo. Overall, we present the first photoactivator of the cGAS‐STING pathway, which may provide an innovative design strategy for anticancer immunotherapy.
The first small molecule that can activate cGAS‐STING in a photocontrollable way is reported. Upon irradiation, Pt1 and Pt2 can damage mitochondrial DNA, the nuclear envelope and nuclear DNA sequentially, which effectively releases DNA into cytoplasm to activate the cGAS‐STING pathway both in vitro and in vivo.
Achieving white‐light emission, especially white circularly polarized luminescence (CPL) from a single‐phase material is challenging. Herein, a pair of chiral CuI coordination polymers (1‐M and 1‐P) ...have been prepared by the asymmetrical assembly of achiral ligands and Cu2I2 clusters. The compounds display dual emission bands and can be used as single‐phase white‐light phosphors, achieving a “warm”‐white‐light‐emitting diode with an ultra‐high color rendering index (CRI) of 93.4 and an appropriate correlated color temperature (CCT) of 3632 K. Meanwhile, corresponding CPL signals with maximum dissymmetry factor |glum|=8×10−3 have been observed. Hence, intrinsic white‐light emission and CPL have been realized simultaneously in coordination polymers for the first time. This work gains insight into the nature of chiral assembly from achiral units and offers a prospect for the development of single‐phase white‐CPL materials.
A pair of chiral CuI coordination polymers (1‐P/M) were produced from achiral precursors by crystallization‐driven symmetry‐breaking assembly. The enantiomers feature unique helical layered structures and tunable dual‐emission photoluminescence, achieving intrinsic “warm”‐white emitting with an ultra‐high color rendering index (93.4) and circularly polarized luminescence with a remarkable dissymmetry factor (8×10−3) simultaneously.
During autophagy, the intracellular components are captured in autophagosomes and delivered to lysosomes for degradation and recycling. Changes in lysosomal trafficking and contents are key events in ...the regulation of autophagy, which has been implicated in many physiological and pathological processes. In this work, two iridium(III) complexes (LysoIr1 and LysoIr2) are developed as theranostic agents to monitor autophagic lysosomes. These complexes display lysosome‐activated phosphorescence and can specifically label lysosomes with high photostability. Simultaneously, they can induce autophagy potently without initiating an apoptosis response. We demonstrate that LysoIr2 can effectively implement two functions, namely autophagy induction and lysosomal tracking, in the visualization of autophagosomal–lysosomal fusion. More importantly, they display strong two‐photon excited fluorescence (TPEF), which is favorable for live cell imaging and in vivo applications.
Kill Two Birds with One Stone: Two iridium(III) complexes can specifically image lysosomes and induce an autophagic response in live cells. The combination of these two intriguing properties makes them ideal theranostic agents to track lysosomal changes during autophagic processes. Additionally, these complexes display strong two‐photon excited fluorescence, which is favorable for live cell imaging and in vivo applications.
The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria‐targeted rhenium(I) complex (DFX‐Re3), integrating the clinical iron ...chelating agent deferasirox (DFX), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX‐Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX‐Re3 affects the events related to apoptosis, RNA polymerases, and T‐cell receptor signaling pathways. Finally, it is shown that DFX‐Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.
Reported here is a mitochondria‐targeted ReI complex, DFX‐Re3, that can relocate iron to the mitochondria and change the metabolites related to epigenetics. DFX‐Re3 can elevate the methylation levels of histone/DNA/RNA, affect RNA polymerase activities, and induce immunogenic apoptosis. This study provides a new approach to the design of epigenetic drugs for recoding the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.
Phosphorescent metal complexes are a new kind of multifunctional antitumor compounds that can integrate imaging and antitumor functions in a single molecule. In this minireview, we summarize the ...recent research progress in this field, concentrating on the theranostic applications of phosphorescent iridium(
iii
), ruthenium(
ii
) and rhenium(
i
) complexes. The molecular design that affords these complexes with tumour- or subcellular organelle-targeting properties is elucidated. The potential of these complexes to induce and monitor the dynamic behavior of subcellular organelles and the changes in microenvironment during the process of therapy is demonstrated. Moreover, the potential and advantages of applying new technologies, such as super-resolution imaging and phosphorescence lifetime imaging, are also described. Finally, the challenges faced in the development of novel theranostic metallo-anticancer complexes for possible clinical translation are proposed.
The recent development in phosphorescent iridium, ruthenium and rhenium complexes as theranostic anticancer agents is summarized.
Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene‐containing Ir(III) photosensitizer (IrFc1) that can ...bind with transferrin and be transported into triple‐negative breast cancer (TNBC) cells via a transferrin receptor‐mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self‐amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T‐cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule‐based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self‐amplifying process.
A Ir(III)‐based photosensitizer with self‐amplifying properties is reported in this work. IrFc1 can cause lipid oxidation leading to ferroptosis in transferrin receptor overexpressing cancer cells, which envokes intense anticaner immnuoenhancement both in vitro and in vivo.
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