Designing luminescent ruthenium prodrug for precise cancer therapy and rapid clinical diagnosis

Zhao, Zhennan; Zhang, Xiang; Li, Chang-e; Chen, Tianfeng

doi:10.1016/j.biomaterials.2018.12.002

Cited by 60 publications

(50 citation statements)

References 38 publications

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“…Further studies were also carried out to examine the effects of the matter forms (metallopolymer and monomeric complex) on the anticancer activity of [CuCl(pip) 2 ]Cl, by in vitro and in vivo models as previously described [39,47]. As shown in Figure 9a, the metallopolymer demonstrated much higher anticancer activities against the tested cancer cells than the monomeric complex.…”

Section: Cell Proliferation Inhibition Of Metallopolymermentioning

confidence: 95%

“…Study has showed a low-molecular-weight metallopolymer in nanofiber form demonstrating potent anticancer properties. [17,36] Nano-formulation has been showed to be able to improve the stability and selectivity of metal complexes, and hence emerges as an appealing strategy to increase anticancer activity and reduce their toxic side effects [37][38][39]. For example, Wu et al have synthesized photosensitive triblock copolymers, which can be self-assembled to form polymer nanosystems to improve their biocompatibility and prolong their blood circulation time to achieve the purpose of regional enrichment of tumor tissue.…”

Section: Introductionmentioning

confidence: 99%

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Self-Assembled Copper Polypyridyl Supramolecular Metallopolymer Achieving Enhanced Anticancer Efficacy

Xiong¹,

Lai²,

Chen³

2020

Self-Assembly of Nanostructures and Patchy Nanoparticles

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Metallopolymers, a combination of organic polymers and metal center, contain metal atoms in repeating monomers can change its dynamic and thermodynamic properties through the directionality of coordination bonds and chemical tailoring of ligands. In the past decade, self-assembled functional supramolecular metallopolymers have aroused a surge of research interest, and have demonstrated application potential in cancer therapy. In this chapter, we have summarized the progress in the rational design of biological application of different metallopolymers. Especially, a copper polypyridyl complex was found be able to self-assemble into a supramolecular metallopolymer driven by the intermolecular interactions, which could enhance the uptake in cancer cells through endocytosis, thus effectively inhibit tumor growth in vivo without damage to the major organs. This study may provide a good example to use self-assembled metallopolymer to achieve enhanced anticancer efficacy.

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Section: Cell Proliferation Inhibition Of Metallopolymermentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Self-Assembled Copper Polypyridyl Supramolecular Metallopolymer Achieving Enhanced Anticancer Efficacy

Xiong¹,

Lai²,

Chen³

2020

Self-Assembly of Nanostructures and Patchy Nanoparticles

Self Cite

View full text Add to dashboard Cite

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“…For example, ruthenium complexes induced cell death might involve the mitochondria-mediated signaling pathway, the death receptor-mediated signaling pathway, and the endoplasmic reticulum signaling pathways (15)(16)(17)(18). Accordingly, the various targets of ruthenium complexes for cell death are mitochondria, endoplasmic reticulum, and multiple molecules (19)(20)(21)(22)(23). In addition, some ruthenium complexes can act as radiosensitizers, theranostic agents, photothermal therapy (PTT) agents, and photodynamic therapy (PDT) agents (24,25).…”

Section: Introductionmentioning

confidence: 99%

Combination of Ruthenium Complex and Doxorubicin Synergistically Inhibits Cancer Cell Growth by Down-Regulating PI3K/AKT Signaling Pathway

et al. 2020

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Combinational use of drugs has been a common strategy in cancer treatment because of synergistic advantages in reducing dose and toxicity, minimizing or delaying drug resistance. To improve the efficacy of chemotherapy, various potential combinations have been investigated. Ruthenium complex is considered a potential alternative of the platinum-based drugs due to its significant efficacy and safety. Previously, we reported that ruthenium(II) complex ( -Ru1) has great anticancer potential and minor toxicity toward normal tissues. However, the therapeutic efficacy and mechanism of action of ruthenium(II) complex combined with other anticancer drugs is still unknown. Here, we investigated the combinational effect of -Ru1 and doxorubicin in different cancer cells. The data assessed by Chou-Talalay method showed significant synergism in MCF-7 cells. Furthermore, the results in antiproliferation efficacy indicated that the combination showed strong cytotoxicity and increasing apoptosis of MCF-7 cells in 2D and 3D multicellular tumor spheroids (MCTSs). Significant inhibition of MCF-7 cells accompanied with increased ROS generation was observed. Furthermore, the expression of PI3K/AKT was significantly down-regulated, while the expression of PTEN was strongly up-regulated in cells treated with combination of -Ru1 and doxorubicin. The expression of NF-κB and XIAP decreased while the expression of P53 increased and associated with apoptosis. These findings suggest that the combination of ruthenium complex and doxorubicin has a significant synergistic effect by down-regulating the PI3K/AKT signaling pathway in MCF-7 cells. This study may trigger more research in ruthenium complex and combination therapy that will be able to provide opportunities for developing better therapeutics for cancer treatment.

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“…53 Capitalizing on these results, a conjugate consisting of a RGD peptide and a Ru(II) polypyridine was recently reported as a selective prodrug. 54 As a different type of delivery system, the conjugation of a Ru(II) polypyridine complex to an epidermal growth factor receptor specific nanobody was shown to have high selectivity for this receptor. 55 Recently the conjugation of a Ru(II) polypyridine to the blood plasma protein serum albumin as a mitochondria selective delivery system was reported.…”

Section: Introductionmentioning

confidence: 99%

Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted 1- and 2-Photon Photodynamic Therapy

Karges¹,

Li²,

Zeng³

et al. 2020

Preprint

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Photodynamic therapy is a medical technique, which is gaining increasing attention to treat various types of cancer. Among the investigated classes of photosensitizers, the use of Ru(II) polypyridine complexes is gaining momentum. However, the currently investigated compounds generally show poor cancer cell selectivity. As a consequence, high drug doses are needed, which can cause side effects. To overcome this limitation, there is a need for the development of a suitable drug delivery system to increase the amount of PS delivered to the tumor. Herein, we report on the encapsulation of a promising Ru(II) polypyridyl complex into polymeric nanoparticles with terminal biotin groups. Thanks to this design, the particles showed much higher selectivity for cancer cells in comparison to non-cancerous cells in a 2D monolayer and 3D multicellular tumor spheroid model. As a highlight, upon intravenous injection of an identical amount of the Ru(II) polypyridine complex, an improved accumulation inside an adenocarcinomic human alveolar basal epithelial tumor of a mouse by a factor of 8.7 compared to the Ru complex itself was determined. The nanoparticles were found to have a high phototoxic effect upon 1-photon (500 nm) or 2-photon (800 nm) excitation with an eradication of an adenocarcinomic human alveolar basal epithelial tumor inside a mouse. Overall, this work describes, to the best of our knowledge, the first <i>in vivo</i> study demonstrating the cancer cell selectivity of a very promising Ru(II)-based PDT photosensitizer encapsulated into polymeric nanoparticles with terminal biotin groups.

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Designing luminescent ruthenium prodrug for precise cancer therapy and rapid clinical diagnosis

Cited by 60 publications

References 38 publications

Self-Assembled Copper Polypyridyl Supramolecular Metallopolymer Achieving Enhanced Anticancer Efficacy

Self-Assembled Copper Polypyridyl Supramolecular Metallopolymer Achieving Enhanced Anticancer Efficacy

Combination of Ruthenium Complex and Doxorubicin Synergistically Inhibits Cancer Cell Growth by Down-Regulating PI3K/AKT Signaling Pathway

Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted 1- and 2-Photon Photodynamic Therapy

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