Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy

Zhou, Zhixuan; Liu, Jiangping; Rees, Thomas W.; Wang, Heng; Li, Xiaopeng; Chao, Hui; Stang, Peter J.

doi:10.1073/pnas.1802012115

Cited by 153 publications

(109 citation statements)

References 42 publications

(75 reference statements)

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…building blocks and Lewis-basic organic donor building blocks via coordination interactions, is a modular approach for the synthesis of discrete supramolecular coordination complexes (SCCs) with high structural and functional complexity (34)(35)(36)(37). By judicious selection of the molecular building blocks, the shapes, geometries, and biological properties of the SCCs can be precisely modulated to promote biomedical applications, such as anticancer activity (38)(39)(40)(41)(42), drug delivery (43)(44)(45)(46), bioimaging (47,48), and biorecognition (49)(50)(51). Self-assembled metallacycles have shown potential as photosensitizers for catalysis as well as PDT for cancer therapy and bacterial inactivation (39,40,(52)(53)(54).…”

Section: Significancementioning

confidence: 99%

“…By judicious selection of the molecular building blocks, the shapes, geometries, and biological properties of the SCCs can be precisely modulated to promote biomedical applications, such as anticancer activity (38)(39)(40)(41)(42), drug delivery (43)(44)(45)(46), bioimaging (47,48), and biorecognition (49)(50)(51). Self-assembled metallacycles have shown potential as photosensitizers for catalysis as well as PDT for cancer therapy and bacterial inactivation (39,40,(52)(53)(54). We envisioned that SCCs with a high level of structural complexity, such as metallacages, could provide favorable photophysical and biological properties over their 2D counterparts due to their 3D structure and high number of functional moieties within the same ensemble.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

Zhou

Liu

Huang³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

124

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is a treatment procedure that relies on cytotoxic reactive oxygen species (ROS) generated by the light activation of a photosensitizer. The photophysical and biological properties of photosensitizers are vital for the therapeutic outcome of PDT. In this work a 2D rhomboidal metallacycle and a 3D octahedral metallacage were designed and synthesized via the coordination-driven self-assembly of a Ru(II)-based photosensitizer and complementary Pt(II)-based building blocks. The metallacage showed deep-red luminescence, a large 2-photon absorption cross-section, and highly efficient ROS generation. The metallacage was encapsulated into an amphiphilic block copolymer to form nanoparticles to encourage cell uptake and localization. Upon internalization into cells, the nanoparticles selectively accumulate in the lysosomes, a favorable location for PDT. The nanoparticles are almost nontoxic in the dark, and can efficiently destroy tumor cells via the generation of ROS in the lysosomes under 2-photon near-infrared light irradiation. The superb PDT efficacy of the metallacage-containing nanoparticles was further validated by studies on 3D multicellular spheroids (MCS) and in vivo studies on A549 tumor-bearing mice.

show abstract

Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

Zhou

Liu

Huang³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

124

View full text Add to dashboard Cite

show abstract

“…Recent research found that OM is susceptible to reactive oxygen species (ROS), and the Gram‐ bacteria is easier to be killed in an oxidative stress environment . Although various ROS producing agents are available, such as graphene and its derivatives, iron nanoparticles, noble metal, or doping titanium oxides, it remains a challenge to design a broad‐spectrum antibacterial surface fulfilling the various requirements of titanium implants. For instance, the developed surface must be biocompatible.…”

Section: Introductionmentioning

confidence: 99%

Corrosion Motivated ROS Generation Helps Endow Titanium with Broad‐Spectrum Antibacterial Abilities

Wang

Qiu

et al. 2019

Adv Materials Inter

View full text Add to dashboard Cite

Materials that spontaneously generate reactive oxygen species (ROS) possess various industrial applications, such as organocatalysis, wastewater, and waste gas government. Given that bacteria, especially the more resistant Gram‐negative (Gram‐) species, are sensitive to ROS, endowing biomaterials with ROS producing abilities may be a useful strategy to fight against bacteria. Herein a minocycline‐loaded Mg–Fe layered double hydroxides film is constructed on the surface of biomedical titanium. The prepared films possess excellent ROS generating capabilities driven by the corrosion process of titanium, which can continuously release hydroxyl radicals without external stimuli. Both Gram‐positive (Gram+) Staphylococcus aureus and (Gram‐) Escherichia coli cells can be killed by the constructed platform under the synergistic effect of the released minocycline and ROS. Besides, the in vitro cell culture assay reveals good cytocompatibility of the as‐prepared films.

show abstract

“…Apart from Ir-based metal complexes, Ru complexes are widely employed for PDT studies [60]. Cationic lipophilic Ru complexes can localize inside the mitochondria.…”

Section: Mitochondria-targeted Metal Complexes For Pdtmentioning

confidence: 99%

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

Jeena

Kim

Jin

et al. 2019

Cancers

106

View full text Add to dashboard Cite

The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches.In healthy cells, mitochondria execute a controlled regulation of multiple functions to maintain the cellular growth-death cycle. However, in the case of tumor cells, to meet the higher metabolic demand of rapidly proliferating cells, dysregulation of mitochondrial metabolism occurs [14,15]. The difference between cancer cell mitochondria and normal cells includes several functional alterations, such as mutation of mtDNA that lead to OXPHOS (oxidative phosphorylation) inhibition and thus deficient respiration and ATP generation, mutation of mtDNA-encoded mitochondrial enzymes, such as SDH (succinate dehydrogenase), IDH1 (isocitrate dehydrogenase 1), IDH2 (isocitrate dehydrogenase 2) [16], and structural differences, such as higher membrane potential of cancer cell mitochondria and higher basicity inside the mitochondrial lumen. The evasion of cell death or inhibition of mitochondria-mediated apoptosis is a hallmark for cancer. Mitochondria generate ROS, which is necessary for signaling under normal conditions. However, when apoptosis is inhibited in the case of cancer, ROS contributes to the neoplastic transformation. Furthermore, for supporting tumor cell survival under harsh tumorigenic conditions, such as nutrient depletion and hypoxia, mitochondria provide flexibility in several pathways either by up-or downregulation [17]. This altered mitochondrial metabolism of cancer cells compared with that of their normal counterparts is advantageous for the selective targeting of cancer mitochondria in therapeutics, which focuses on the cancer mitochondria specific features [18]. Directing the therapeutic agent to the mitochondria is an efficient way of eliminating cancer cells because the designed drug molecules could act at the central point of the cell, and therefore, engineering mitochondrial-targeted therapeutic agents have gained much interest in cancer thera...

show abstract

Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy

Cited by 153 publications

References 42 publications

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

Corrosion Motivated ROS Generation Helps Endow Titanium with Broad‐Spectrum Antibacterial Abilities

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

Contact Info

Product

Resources

About