Tumor metastases account for nearly 90% of cancer-related fatalities. To tackle this issue, chemotherapeutic agents that induce immunogenic cell death (ICD) are being investigated as promising candida Show more
Tumor metastases account for nearly 90% of cancer-related fatalities. To tackle this issue, chemotherapeutic agents that induce immunogenic cell death (ICD) are being investigated as promising candidates for metastatic cancer treatment. Herein, the chemical synthesis and biological evaluation of a novel Ga(III) complex with Schiff bases, [Ga((E)-1-((quinolin-8-ylimino)methyl)naphthalen-2-olato)2][Cl], for potential use in combined chemotherapy and immunotherapy are reported. This compound exhibited broad cytotoxicity against human breast cancer, pancreatic cancer, cervical cancer cell lines, and the noncancerous human fibroblast cell line. Mechanistic investigations revealed that the compound triggers apoptosis and ICD hallmarks, such as translocation of calreticulin, phosphorylation of eIF2α, migration of high mobility group protein 1, and release of adenosine triphosphate. Deeper biological assessment using multicellular tumor spheroids of cervical cancer cell lines, a solid tumor model, demonstrated successful eradication at micromolar concentrations. This study presents one of the few reported Ga(III) complexes capable of inducing immunogenic cell death. Show less
This study presents the chemical synthesis and biological evaluation of a series of gold(I)-N-heterocyclic carbene complexes as potential anticancer agents. The compounds demonstrated broad activity a Show more
This study presents the chemical synthesis and biological evaluation of a series of gold(I)-N-heterocyclic carbene complexes as potential anticancer agents. The compounds demonstrated broad activity against various cancer cell lines, exhibiting cytotoxicity in the low micromolar range. Mechanistic investigations revealed that these complexes preferentially accumulate in the mitochondria of cancer cells, where they induce the generation of reactive oxygen species and lipid peroxides, ultimately triggering ferroptosis. Further studies in multicellular tumor spheroids confirmed the compounds' ability to penetrate three-dimensional cellular structures and effectively eradicate them at low micromolar concentrations. This work represents the first known example of a gold(I)-N-heterocyclic carbene complex inducing ferroptosis, expanding the therapeutic potential of gold(I)-based metallodrugs. Show less
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical inv Show more
Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies. Show less
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly i Show more
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly important role in biomedical research ranging from subcellular level to individual level. The unique properties of BICAs, including expression by cells as reporters and specific genetic modification, facilitate various in vitro and in vivo studies, such as quantification of gene expression, observation of protein interactions, visualization of cellular proliferation, monitoring of metabolism, and detection of dysfunctions. Furthermore, in human body, BICAs are remarkably helpful for disease diagnosis when the dysregulation of these agents occurs and can be detected through imaging techniques. There are various BICAs matched with a set of imaging techniques, including fluorescent proteins for fluorescence imaging, gas vesicles for ultrasound imaging, and ferritin for magnetic resonance imaging. In addition, bimodal and multimodal imaging can be realized through combining the functions of different BICAs, which helps overcome the limitations of monomodal imaging. In this review, the focus is on the properties, mechanisms, applications, and future directions of BICAs. Show less
Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side Show more
Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl] + (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs. Show less