A Series of Planar Phosphorescent Cyclometalated Platinum(II) Complexes as New Anticancer Theranostic Agents That Induce Oncosis

Wang, Wenting; Wang, Pengchao; Liao, Xiali; Yang, Bo; Gao, Chuanzhu; Yang, Jing

doi:10.1021/acs.jmedchem.3c01126

Cited by 12 publications

(1 citation statement)

References 32 publications

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“…The specific operation was as follows: accurately weighed the complexes 1–3 were dissolved in 2 ml of DMF, 8 ml of PBS (PH=7.4) buffer solution was added, ultrasonically shaken to make it fully miscible, and incubated at 37 °C away from light, while 10 ml of PBS buffer (20 % DMF) was configured as a control group. The UV absorption spectra of the compounds were measured by UV spectrophotometer at 0, 12, 24 and 48 h of incubation, respectively [15a,31] …”

Section: Methodsmentioning

confidence: 99%

Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity

Peng,

Shi,

Wang

et al. 2024

ChemistrySelect

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Picoplatin can effectively circumvent cisplatin‐induced resistance through the “steric hindrance effect” of its structure, but there are still problems such as toxicity and side effects, so the search for safer, more efficient platinum analogs is crucial. Here we report three fluorinated pyridine‐containing Pt(IV) complexes employing biotin as an axial ligand to provide targeting functionality. Lipid solubility studies showed that all the synthesized complexes possessed improved lipid‐water partition coefficients, which are beneficial for transmembrane transport of drugs. The DNA binding activity of the compounds was studied using UV titration, fluorescence titration, and PicoGreen staining, demonstrating the presence of potential intercalation and electrostatic interaction binding modes. It probably attributable to planar π‐π interactions provided by the aromatic pyridine ligands. Meanwhile, molecular docking studies showed that the introduction of axial biotin molecules allowed the complexes to effectively target cancer cells, which was simultaneously confirmed by the results of cellular uptake studies. And another docking result showed that the Pt(IV) complexes binds to DNA by minor groove binding. The synthesized complexes exhibited similar cytotoxicity to cisplatin in five cell lines (SW480, HCT116, HepG2, A549 and LO2), with complex 3 being superior to the parent drug, picoplatin.

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Section: Methodsmentioning

confidence: 99%

Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity

Peng,

Shi,

Wang

et al. 2024

ChemistrySelect

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Self‐Assembled Metal Complexes in Biomedical Research

Wang,

Xu,

Tang

et al. 2024

Advanced Materials

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Cisplatin is widely used in clinical cancer treatment; however, its application is often hindered by severe side effects, particularly inherent or acquired resistance of target cells. To address these challenges, an effective strategy is to modify the metal core of the complex and introduce alternative coordination modes or valence states, leading to the development of a series of metal complexes, such as platinum (IV) prodrugs and cyclometalated complexes. Recent advances in nanotechnology have facilitated the development of multifunctional nanomaterials that can selectively deliver drugs to tumor cells, thereby overcoming the pharmacological limitations of metal‐based drugs. This review first explores the self‐assembly of metal complexes into spherical, linear, and irregular nanoparticles in the context of biomedical applications. The mechanisms underlying the self‐assembly of metal complexes into nanoparticles are subsequently analyzed, followed by a discussion of their applications in biomedical fields, including detection, imaging, and antitumor research.

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A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity

Feng,

Tang,

Shu

et al. 2024

Angewandte Chemie

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An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance the immune response. Despite this, there has been limited investigation and reporting on the mechanisms of oncosis and its correlation with immune response. Herein, we designed and synthesized a Ru(II) complex that targeted the nucleus and mitochondria to induce cell oncosis. Briefly, the Ru(II) complex disrupts the nucleus and mitochondria DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption and porimin activation. Concurrently, mitochondrial damage and endoplasmic reticulum stress result in the release of Ca2+ ions and increased expression of Calpain 1. Subsequently, specific pore proteins porimin and Calpain 1 promote cristae destruction or vacuolation, ultimately leading to cell membrane rupture. The analysis of RNA sequencing demonstrates that Ru(II) complex can initiate the oncosis‐associated pathway and activate both innate and adaptive immunity. In vivo experiments have confirmed that oncosis facilitates the maturation of dendritic cells and the awakening of adaptive cytotoxic T lymphocytes but also induces the polarization of tumor‐associated macrophages (TAMs) towards an M1 phenotype and activates the innate immune response of TAMs.

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A Series of Planar Phosphorescent Cyclometalated Platinum(II) Complexes as New Anticancer Theranostic Agents That Induce Oncosis

Cited by 12 publications

References 32 publications

Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity

Synthesis and DNA Interactions Study of Novel Fluorinated Pyridinium Platinum (IV) Complexes with Tumor Targeting Activity

Self‐Assembled Metal Complexes in Biomedical Research

A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity

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