An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer

Wang, Lili; Guan, Ruilin; Xie, Lina; Liao, Xinxing; Xiong, Kai; Rees, Thomas W.; Chen, Yu; Ji, Liang‐Nian; Chao, Hui

doi:10.1002/anie.202013987

Cited by 178 publications

(105 citation statements)

References 73 publications

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“…Immunogenic cell death (ICD) is a form of cell death in which ICD occurs in tumor cells; a series of signaling molecules are involved, including the release of calreticulin (CRT), heat-shock protein (HSP70), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) [ 41 ]. ICD is believed to overcome drug resistance caused by tumor, enhance antitumor immunity, and achieve better therapeutic effect [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

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Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Fu¹,

Xu²,

Liu³

et al. 2022

Molecules

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Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5′,6,6′-tetrachloro-1,1,3′,3′-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism.

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Section: Resultsmentioning

confidence: 99%

“…Next, the secondary antibody FITC-labeled Goat Anti-Rabbit IgG was incubated in darkness for 1 h. The cells were washed three times with PBS. Finally, the nuclei were stained with Hoechst and photographed under Micro XLS System (MD company, San Jose, CA, USA) [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Fu¹,

Xu²,

Liu³

et al. 2022

Molecules

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“…Accumulating studies have combined nanoparticles with immunoadjuvants, chemotherapeutics, photodynamic therapy, or again photothermal therapy in order to reshape the tumor hypoxic microenvironment to elicit or enhance ICD (81,82). These novel nanoparticles synergized with IR and enhanced antitumor immune function (83)(84)(85)(86)(87). Qian Chen et al confirmed that PLGA-R837@Cat nanoparticle-based x-ray radiation inhibited primary tumors significantly in comparison with RT alone.…”

Section: The Methods Of Enhancing Ir-induced Icdmentioning

confidence: 99%

Immunogenic Cell Death Induction by Ionizing Radiation

et al. 2021

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Immunogenic cell death (ICD) is a form of regulated cell death (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), and heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, and the dose, type, and fractionation of irradiation influence the induction of ICD. At present, IR-induced ICD is mainly verified in vitro in mice and there is few clinical evidence about it. To boost the induction of ICD by IR, some strategies have shown synergy with IR to enhance antitumor immune response, such as hyperthermia, nanoparticles, and chemotherapy. In this review, we focus on the molecular mechanisms of ICD, ICD-promoting factors associated with irradiation, the clinical evidence of ICD, and immunogenic forms of cell death. Finally, we summarize various methods of improving ICD induced by IR.

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“…Hence, it is desirable to develop PSs that could target organelles and generate high dosage of 1 O 2 in situ to directly cause dysfunction of subcellular organelles and activate specific cell death signals. Several PSs targeting mitochondria 15 – 17 , endoplasmic reticulum (ER) 18 – 20 , lysosome 21 , 22 and cell membrane 23 , 24 have been reported and exhibited high PDT efficiency. However, due to the lack of effective Golgi apparatus (GA) targeting strategies, specific GA targeting AIEgen-based PSs have seldom been reported.…”

Section: Introductionmentioning

confidence: 99%

Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

et al. 2022

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Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S1) and the lowest triplet state (T1) (ΔEST) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.

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An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer

Cited by 178 publications

References 73 publications

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901

Immunogenic Cell Death Induction by Ionizing Radiation

Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

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