SCPL acyltransferases catalyze the metabolism of chlorogenic acid during purple coneflower seed germination.

The metabolism of massively accumulated chlorogenic acid is crucial for the successful germination of purple coneflower (Echinacea purpurea (L.) Menoch). A serine carboxypeptidase-like (SCPL) acyltransferase (chicoric acid synthase, CAS) utilizes chlorogenic acid to produce chicoric acid during germination. However, it seems that the generation of chicoric acid lags behind the decrease in chlorogenic acid, suggesting an earlier route of chlorogenic acid metabolism. We discovered another chlorogenic acid metabolic product, 3,5-dicaffeoylquinic acid, which is produced before chicoric acid, filling the lag phase. Then, we identified two additional typical clade IA SCPL acyltransferases, named chlorogenic acid condensing enzymes (CCEs), that catalyze the biosynthesis of 3,5-dicaffeoylquinic acid from chlorogenic acid with different kinetic characteristics. Chlorogenic acid inhibits radicle elongation in a dose-dependent manner, explaining the potential biological role of SCPL acyltransferases-mediated continuous chlorogenic acid metabolism during germination. Both CCE1 and CCE2 are highly conserved among Echinacea species, supporting the observed metabolism of chlorogenic acid to 3,5-dicaffeoylquinic acid in two Echinacea species without chicoric acid accumulation. The discovery of SCPL acyltransferase involved in the biosynthesis of 3,5-dicaffeoylquinic acid suggests convergent evolution. Our research clarifies the metabolism strategy of chlorogenic acid in Echinacea species and provides more insight into plant metabolism.

A 700 nm LED light activated Ru(II) complex destroys tumor cytoskeleton via photosensitization and photocatalysis.

Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near-infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, we present an NIR light triggered di-nuclear photoactivable Ru(II) complex (Ru2) and comprehensively investigated the antitumor mechanism. The introduction of a donor-acceptor-donor (D-A-D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime. Most importantly, when activated by 700 nm NIR light, Ru2 exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization and photocatalytic activity to destroy diverse intracellular biomolecules. In vitro and in vivo experiments show that when activated by 700 nm NIR light, Ru2 exhibits nanomolar photocytotoxicity toward 4T1 cancer cells via the induction of calcium overload and endoplasmic reticulum (ER) stress. These findings provide a robust foundation for the development of NIR-activated Ru(II) PACT complexes for phototherapeutic application. This article is protected by copyright. All rights reserved.

An Electron Donor-Acceptor Structured Rhenium(I) Complex Photo-Sensitizer Evokes Mutually Reinforcing "Closed-Loop" Ferroptosis and Immunotherapy.

The hypoxic microenvironment of solid tumors severely lowers the efficacy of oxygen-dependent photodynamic therapy (PDT). The development of hypoxia-tolerant photosensitizers for PDT is an urgent requirement. In this study, a novel rhenium complex (Re-TTPY) to develop a "closed-loop" therapy based on PDT-induced ferroptosis and immune therapy is reported. Due to its electron donor-acceptor (D-A) structure, Re-TTPY undergoes energy transfer and electron transfer processes under 550 nm light irradiation and displays hypoxia-tolerant type I/II combined PDT capability, which can generate 1O2, O2 -, and ·OH simultaneously. Further, the reactive oxygen species (ROSs) leads to the depletion of 1,4-dihydronicotinamide adenine dinucleotide (NADH), glutathione peroxidase 4 (GPX4), and glutathione (GSH). As a result, ferroptosis occurs in cells, simultaneously triggers immunogenic cell death (ICD), and promotes the maturation of dendritic cells (DCs) and infiltration of T cells. The release of interferon-γ (IFN-γ) by CD8+ T cells downregulates the expression of GPX4, further enhancing the occurrence of ferroptosis, and thereby, forming a mutually reinforcing "closed-loop" therapeutic approach.

Self-Assembly of Erlotinib-Platinum(II) Complexes for Epidermal Growth Factor Receptor-Targeted Photodynamic Therapy.

Due to cell mutation and self-adaptation, the application of clinical drugs with early epidermal growth factor receptor (EGFR)-targeted inhibitors is severely limited. To overcome this limitation, herein, the synthesis and in-depth biological evaluation of an erlotinib-platinum(II) complex as an EGFR-targeted anticancer agent is reported. The metal complex is able to self-assemble inside an aqueous solution and readily form nanostructures with strong photophysical properties. While being poorly toxic toward healthy cells and upon treatment in the dark, the compound was able to induce a cytotoxic effect in the very low micromolar range upon irradiation against EGFR overexpressing (drug resistant) human lung cancer cells as well as multicellular tumor spheroids. Mechanistic insights revealed that the compound was able to selectively degrade the EGFR using the lysosomal degradation pathway upon generation of singlet oxygen at the EGFR. We are confident that this work will open new avenues for the treatment of EGFR-overexpressing tumors.

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy.

Photoactive antibacterial therapy is one of the novel therapeutic methods that has great application potential and prospects for curbing bacterial infections. In this work, a photoactivated iridium complex (Ir-Cl) is synthesized for photoactive antibacterial research. Ir-Cl exhibits photoacidolysis, which can generate H+ and be converted into a photolysis product Ir-OH under blue light irradiation. At the meantime, this process is accompanied by 1O2 generation. Notably, Ir-Cl can selectively permeate S. aureus and exhibit excellent photoactive antibacterial activity. Mechanism studies show that Ir-Cl can ablate bacterial membranes and biofilms under light irradiation. Metabolomics analysis proves that Ir-Cl with light exposure mainly disturbs some amino acids' degradation (e.g., valine, leucine, isoleucine, arginine) and pyrimidine metabolism, which indirectly causes the ablation of biofilms and ultimately produces irreversible damage to S. aureus. This work provides guidance for metal complexes in antibacterial application.

A Photoisomerizable Zinc (II) Complex Inhibits Microtubule Polymerization for Photoactive Therapy.

The photoisomerization-induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex (Zn1), which releases its trans ligand (trans-L1) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product (cis-L1) and generate singlet oxygen (1 O2 ). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen-dependent limitation of traditional photodynamic therapy.

Borderland Economic Resilience under COVID-19: Evidence from China-Russia Border Regions.

The COVID-19 pandemic has had a great impact on the global economy and trade, and border regions have been hit severely because of their high dependency on foreign trade. To understand better the economic impact of COVID-19 on border regions, we developed a COVID-19 economic resilience analytical framework and empirically examined 10 Chinese-Russian border cities in Northeast China. We quantitatively analyzed five dimensions of economic resilience, distinguished four types of shock, and examined the determinants of economic resilience. The results show that: (1) the COVID-19 pandemic has wide-ranging impacts in the border areas, with import-export trade and retail sales of consumer goods being the most vulnerable and sensitive to the shock. The whole economy of the border areas is in the downward stage of the resistance period; (2) from a multi-dimensional perspective, foreign trade and consumption are the most vulnerable components of the borderland economic system, while industrial resilience and income resilience have improved against the trend, showing that they have good crisis resistance; (3) borderland economic resilience is a spatially heterogeneous phenomenon, with each border city showing different characteristics; (4) economic openness, fiscal expenditure, and asset investment are the key drivers of economic resilience, and the interaction between the influencing factors presents a nonlinear and bi-factor enhancement of them. The findings shed light on how border economies can respond to COVID-19, and how they are useful in formulating policies to respond to the crisis.

A Photoactivated Sorafenib-Ruthenium(II) Prodrug for Resistant Hepatocellular Carcinoma Therapy through Ferroptosis and Purine Metabolism Disruption.

The curative effect of sorafenib in hepatocellular carcinoma (HCC) is limited and sorafenib resistance remains a major obstacle for HCC. To overcome this obstacle, a new photoactive sorafenib-Ru(II) complex Ru-Sora has been designed. Upon irradiation (λ = 465 nm), Ru-Sora rapidly releases sorafenib and generates reactive oxygen species, which can oxidize intracellular substances such as GSH. Cellular experiments show that irradiated Ru-Sora is highly cytotoxic toward Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared to sorafenib, Ru-Sora has a significant photoactivated chemotherapeutic effect against Hep-G2-SR cancer cells and 3D Hep-G2 multicellular tumor spheroids. Furthermore, Ru-Sora inducing apoptosis and ferroptosis is proved by GSH depletion, GPX4 downregulation, and lipid peroxide accumulation. Metabolomics results suggest that Ru-Sora exerts photocytotoxicity by disrupting the purine metabolism, which is expected to inhibit tumor development. This study provides a promising strategy for enhancing chemotherapy and combating drug-resistant HCC disease.

Ferroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.

Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)-cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (1O2) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. In vivo studies further demonstrate that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT in vivo. This is the first example of platinum(ii) complexes for sonodynamic therapy. This work extends the biological applications of metal complexes from PDT to SDT.

Cross-Border Accessibility and Spatial Effects of China-Mongolia-Russia Economic Corridor under the Background of High-Speed Rail Environment.

Under the background of "the Belt and Road" and "China-Mongolia-Russia economic corridor" initiatives, we studied the urban accessibility level and regional spatial effect of the west line and east line of China-Mongolia-Russia economic corridor in the high-speed rail (HSR) environment. The results are as following. (1) The operation of China-Mongolia-Russia HSR will greatly improve the urban accessibility level, which will shorten the whole journey time to two days along China-Mongolia-Russia economic corridor. The regional space-time convergence effect will be very strong in the China-Mongolia-Russia HSR environment. (2) The accessibility level and its improvement degree of the China-Mongolia-Russia east line are stronger than those of the west line. The accessibility level of different countries differs: China > Russia > Mongolia. The accessibility improvement degree of different countries also differs: Mongolia > Russia > China. Spatially, the accessibility improvement degree of the cities, which are located in the middle of the line is stronger than those cities at the beginning and end of the line. (3) Affected by the China-Mongolia-Russia HSR environment, the spatial polarization effect of China-Mongolia-Russia HSR axial belt will be further enhanced. The internal boundary effect of the China-Mongolia-Russia HSR axial belt will disappear. New HSR economic growth poles will occur, promoting the formation of point-axis system. China-Mongolia-Russia cross-border trade creation and transfer effects will be deepened.

What Affects the Economic Resilience of China's Yellow River Basin Amid Economic Crisis-From the Perspective of Spatial Heterogeneity.

This paper contributes to the study of regional economic resilience by analyzing the dynamic characteristics and influence mechanisms of resilience from the perspective of spatial heterogeneity. This paper focuses on the resistance and recoverability dimensions of resilience and analyzed the dynamic changes in economic resilience in China's Yellow River Basin in response to the 2008 economic crisis. The multi-scale geographical weighted regression model was utilized to examine the effect of key factors on regional economic resilience. Our findings show the following: (1) The resistance of the Yellow River Basin to the financial crisis was high; however, the recoverability decreased significantly over time. (2) The spatial heterogeneity of driving factors was significant, and they had different effect scales on economic resilience. Related variety, government agency, environment, and opening to the global economy had a significant effect on economic resilience only in a specific small range. Specialization, unrelated variety, and location had opposite effects in different regions of the Yellow River Basin. (3) Specialization limited the area's resistance to shock but enhanced the recoverability. Related variety improved regional economic resilience. Unrelated variety was not conducive to regional resistance to shock and had opposite effects on the recoverability in different regions. (4) Government agency and financial market promoted regional economic resilience. Environment pollution and resource-based economic structure limited regional economic resilience. Opening to the global economy and urban hierarchy limited regional resistance to shock, but strong economic development had the opposite effect of improved regional resistance. The location in the east of the Yellow River Basin enhanced the recoverability; however, the location in the west limited the recoverability.

Spatiotemporal evolution characteristics of coordinated development of urbanization and ecological environment in eastern Russia-Perspectives from the 3D global trend and 2D plane analysis.

Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it has great value to study the temporal and spatial evolution characteristics of the coordinated development between the urbanization and ecological environment in eastern Russia (the Siberian Federal District and the Far East Federal District). In this paper, we studied the urbanization development level, eco-environment development level, and their coupling coordinated development degree during 2005-2018 in the eastern Russia from the perspectives of the 3D global trend and 2D plane analysis. First, combining with the Population-Economic-Sociology and Pressure-State-Response models, the urbanization development level and eco-environment development level were calculated by the comprehensive weighting method of entropy weight and variation coefficient for eastern Russia. Second, the coupling coordinated development degree of the urbanization development level and eco-environment development level was measured by the coupling coordination model for eastern Russia. Finally, the spatial differentiation of the urbanization development level, the eco-environment development level and their coupling coordinated development degree was performed respectively by the 3D global trend and 2D plane analysis using ArcGIS. The results are as following. First, the comprehensive urbanization development level of eastern Russia has increased from 2005 to 2018, and the economic urbanization is the main factor that affects the urbanization development in eastern Russia. The comprehensive eco-environment development level of eastern Russia has decreased from 2005 to 2018, and the eco-environment pressure is the main factor that affects the eco-environment development in eastern Russia. The coupling coordination degree of the urbanization development and eco-environment development has increased from 2005 to 2018. However, it is still in the uncoordinated stage. Second, from 2005 to 2018, the urbanization development level of the Siberian Federal District is higher than that of the Far East Federal District. The eco-environment development level of the Siberian Federal District is balanced to that of the Far East Federal District. The coupling coordination degree of the Siberian Federal District is higher than that of the Far East Federal District. Among the Siberian and Far East Federal Districts, most of the federal subjects belong to the uncoordinated stage of the urbanization development and the eco-environment development. Third, the urbanization development level, the eco-environment development level, and their coupling coordinated development level are all spatially imbalanced in the eastern Russia, which show the "High West, Low East" and "High Center, Low North and Low South" spatial pattern from the perspectives of the 3D global trend and 2D plane analysis. The areas with high levels are concentrated in the Novosibirsk Region, Altay Territory, Kemerovo Region, Krasnoyarsk Territory, and Irkutsk Region. The areas with low ones are mostly in the Republic of Altay and Chukotka Autonomous Area. Finally, we suggest policies and strategies that can boost the growth and development of the urbanization and the eco-environment in the Sino-Russian border areas.

An osmium-peroxo complex for photoactive therapy of hypoxic tumors.

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O2•- upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

Spatiotemporal evolution characteristics of urbanization and its coupling coordination degree in Russia - perspectives from the population, economy, society, and eco-environment.

Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it is of great significance to study the temporal and spatial evolution characteristics of urbanization in Russia. This paper studied the population urbanization level, economic urbanization level, social urbanization level, eco-environment urbanization level, and their coupling coordination development degree during 2005-2020 in Russia. First, combining with the Population-Economic-Sociology-Eco-environment model, the paper constructed the index systems to evaluate the urbanization development levels in Russia. Second, based on the comprehensive weighting method of entropy weight and variation coefficient, this paper calculated the population urbanization level, economic urbanization level, social urbanization level, and eco-environment urbanization level in Russia. Third, this paper used the coupling coordination model to measure the coupling coordination degree of the urbanization development levels in Russia. Finally, the spatial differentiation of the population urbanization level, economic urbanization level, social urbanization level, eco-environment urbanization level, and their coupling coupling-coordination degree was performed, respectively, by using ArcGIS. The results are as the following. First, from 2005 to 2020, the economic urbanization level and eco-urbanization level have shown the increasing trend in Russia. The population urbanization level and social urbanization level have shown the stable changing trend in Russia. The eco-environment urbanization and economic urbanization contribute larger share to the urbanization system compared with the population urbanization and social urbanization. The coupling coordination development degree of population urbanization level, economic urbanization level, social urbanization level, and eco-environment urbanization level has showed a slight increasing trend. However, the overall situation of the urbanization in Russia is still in the moderate uncoordinated recession stage. Second, the federal subjects with high urbanization development levels are mainly distributed in Moscow city, Moscow Region, Sverdlovsk Region, Tumen Region, Saint-Petersburg city, Republic of Tatarstan, Krasnoyarsk Territory, Republic of Bashkortostan, Chelyabinsk Region, Nizhny Novgorod Region, Krasnodar Territory, Rostov Region, and Khanty-Mansiysky Autonomous Area. The federal subjects with low ones are mainly located in Republic of Khakasia, Republic of Marii El, Republic of Kabardino-Balkaria, Republic of Tyva, Republic of Karachaevo-Cherkessia, Republic of Kalmykia, Republic of Altay, Jewish Autonomous Area, and Republic of Ingushetia. Third, spatially, from 2005 to 2020, the urbanization pattern of population, economy, society, eco-environment, and their coupling coordination degree in Russia all show unbalanced development characteristics. The population urbanization pattern and the social urbanization pattern have not changed significantly, showing the spatial characteristics of "high west, low east," and "high middle, low north, low south." The economic urbanization pattern has been increasing significantly, showing the spatial characteristics of "high core, low edge." The eco-environment urbanization pattern has not changed significantly, showing the spatial characteristics of "high north, low south." The coupling coordinated development degree of urbanization pattern has showed a slight increasing trend, showing the spatial characteristics of "high middle, low north, low south," "high west, low east". Finally, we suggest policies and strategies that can boost the growth and development of the urbanization in Russia.

Evolution characteristics of temporal and spatial pattern of Russian economic differences since the 21st century.

Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it is of great significance to study the temporal and spatial economic pattern in the Russian Federation. Based on the economic development difference index, regional economic grade index, global trend analysis tool and spatial autocorrelation model, this paper analyzes the temporal and spatial pattern evolution characteristics of Russian economic differences from 2002 to 2020. The results are as following. First, although the economic imbalance among various federal subjects has been decreasing, the economic polarization has been still severe between the prosperous developed regions and the stagnant backward regions during 2002-2020. Russia's economy shows a trend of changing from significant positive correlation in strong agglomeration space to positive correlation in weak agglomeration space, and then to random distribution. Second, there has been great differences of the economic development among various federal subjects. The economic grade of the Russian federal subjects presents a significant spatial differentiation pattern. The Russian Federation's economic resources are concentrated in the first-class federal subject (Moscow City), second-class federal subjects (Tumen Region, Moscow Region and Saint-Petersburg city) and a few third-class federal subjects (Yamalo-Nenetsky Autonomous Area, Khanty-Mansiysky Autonomous Area, Republic of Tatarstan, Krasnodar Territory, Sverdlovsk Region, etc). Third, the Russian Federation's economy presents "High Core, Low Periphery", "High West, Low East" and "High south, Low north" spatial differentiation pattern. The economic hot regions coincide with the high-class economic regions, which are mainly distributed in the contiguous areas of Ural Federal District and Volga Federal District, as well as the Moscow City, Moscow Region, Saint-Petersburg city, Krasnodar Territory and Rostov Region. The economic cold regions coincide with the low-class economic regions, which are mainly located in the Far East Federal District, the east of Siberian Federal District, the north of North West Federal District and the south of North-Caucasian Federal District. Finally, we suggest the recommendation for policy makers in Russia. And we propose the future research ideas.

An ultrasound activated cyanine-rhenium(I) complex for sonodynamic and gas synergistic therapy.

A novel cyanine-rhenium(I) tricarbonyl complex is developed as a potent sonosensitizer and sono-activatable CO-releasing agent for synergistic sonodynamic therapy and CO gas therapy of cancer. The complex induced ferroptosis as the mode of cell death.

Substrate promiscuity of acyltransferases contributes to the diversity of hydroxycinnamic acid derivatives in purple coneflower.

High pliability and promiscuity are observed widely exist in plant specialized metabolism, especially the hydroxycinnamic acid metabolism. Here, we identified an addition BAHD acyltransferase (EpHMT) that catalyzes phaselic acid biosynthesis and found that the substrate promiscuities of identified BAHD and SCPL acyltransferases are responsible for the diversity of hydroxycinnamic acid derivatives in purple coneflower.

Spatial Distribution Pattern Evolution of the Population and Economy in Russia since the 21st Century.

Under the background of "the Belt and Road" and "China, Mongolia and Russia economic corridor" initiatives, this paper studied the spatial distribution pattern evolution of population and economy in Russia since the 21st century, which could provide implications for the regional development planning, economic optimization layout, energy resource development, transportation infrastructure construction between China and Russia. Combined with the panel data of population, GDP, land area, etc., we used the gravity center analysis, geographic concentration degree, and inconsistency index to study Russia's population pattern evolution trend, economic pattern evolution trend, spatial inconsistency types of population distribution and economic development. The results and conclusions are as follows. Russia's population and economic gravity centers have migrated towards the northwest direction. Russia's population and economic distribution pattern presents the unbalanced development trend, which could be characterized by the differentiation pattern of "High West, Low East" and "High South, Low North" divided by the Ural Federal District. In the southwest areas of Russia, the population concentration degree is higher than the economic concentration degree in most federal subjects. In the northeast areas of Russia, the economic concentration degree is higher than the population concentration degree in most federal subjects.

Highly Efficient Ir(III)-Coumarin Photo-Redox Catalyst for Synergetic Multi-Mode Cancer Photo-Therapy.

Four photo-catalysts of the general formula [Ir(CO6/ppy)2 (L)]Cl where CO6=coumarin 6 (Ir1-Ir3), ppy=2-phenylpyridine (Ir4), L=4'-(3,5-di-tert-butylphenyl)-2,2' : 6',2''-terpyridine (Ir1), 4'-(3,5-bis(trifluoromethyl)phenyl)-2,2' : 6',2''-terpyridine (Ir2 and Ir4), and 4-([2,2' : 6',2''-terpyridin]-4'-yl)-N,N-dimethylaniline (Ir3) were synthesized and characterized. These photostable photo-catalysts (Ir1-Ir3) showed strong visible light absorption between 400-550 nm. Upon light irradiation (465 and 525 nm), Ir1-Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1-Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models.

A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy.

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. However, sonodynamic therapy (SDT) performance of [Ru(bpy)3]2+ has not been investigated so far. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Here, we report that [Ru(bpy)3]2+ is a highly potent sonosensitizer and sonocatalyst for sonotherapy in vitro and in vivo. [Ru(bpy)3]2+ can produce singlet oxygen (1O2) and sono-oxidize endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) under ultrasound (US) stimulation in cancer cells. Furthermore, [Ru(bpy)3]2+ enables effective destruction of mice tumors, and the therapeutic effect can reach deep tissues over 10 cm under US irradiation. This work paves a way for polypyridinal metal complexes to be applied to the noninvasive precise sonotherapy of cancer.