Multifunctional Ru(III)/FeO/DNA nanoplatform for photothermal-enhanced photodynamic and chemodynamic cancer therapy.

Among the many cancer treatment methods, there have been many reports on the use of nanoplatforms with single treatment methods such as photothermal, photodynamic or chemodynamic for cancer treatment. In this study, Ru(III) with photodynamic effect and FeO nanoparticles with photothermal and chemodynamic effects are connected through long DNA chains with efficient active targeting rolling circle amplification to construct Ru(III)/FeO/DNA nano-platform realizes the combination of photothermal, photodynamic and chemodynamic treatment, which significantly improves the therapeutic effect of the nano-platform. Its multiple active targeting capabilities reduce the damage to normal cells.

Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells.

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287.

A photo-degradable BODIPY-modified Ru(II) photosensitizer for safe and efficient PDT under both normoxic and hypoxic conditions.

Photodynamic therapy (PDT) is promising for cancer treatment but still suffers from some limitations. For instance, PDT based on O generation (in a type-II mechanism) is heavily dependent on high oxygen concentrations and will be significantly depressed in hypoxic tumors. In addition, the residual photosensitizers after PDT treatment may cause severe side-effects under light irradiation.

Nitroreductase-Responsive Photosensitizers for Selective Imaging and Photo-Inactivation of Intracellular Bacteria.

Intracellular Staphylococcus aureus (S. aureus), especially the methicillin resistant staphylococcus aureus (MRSA), are difficult to detect and eradicate due to the protection by the host cells. Antibacterial photodynamic therapy (aPDT) offers promise in treating intracellular bacteria, provided that selective damage to the bacteria ranther than host cells can be realized.

A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics.

The ruthenium polypyridine complex [Ru(dppa)(pytp)] (PF) (termed as ZQX-1), where dppa = 4,7-diphenyl-1,10-phenanthroline and pytp = 4'-pyrene-2,2':6',2''-terpyridine, has been shown a high and selective cytotoxicity to hypoxic and cisplatin-resistant cancer cells either under irradiation with blue light or upon two-photon excitation. The IC values of ZQX-1 towards A549 cancer cells and HEK293 health cells are 0.16 ± 0.

Ru(II) Complexes with Enaminone Structures for Rapid Sterilization of Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance.

Drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a serious threat to human life. Therefore, there is urgent need to develop antibiotics with new chemical structures and antibacterial mechanisms, especially those that elicit little drug resistance after long-term use. Herein we synthesized three novel ruthenium complexes (Ru1-Ru3) containing the enaminone structures for the first time.

Electronic effects on polypyridyl Co complex-based water reduction catalysts.

Three new isomeric cobalt complexes of TPA (tris(2-pyridylmethyl)amine) based on methoxy substitution at the , and positions, respectively, were constructed and their photocatalytic proton reduction efficiencies were compared. It was found that there are good linear correlations with the Hammett constants of the substituents for the computed Co-N bond lengths, redox potentials of Co and Co events, and the photocatalytic activities of the complexes. The -substituted Co complex distinguished itself from the others remarkably in all these comparisons, demonstrating the presence of a steric effect besides the electronic effect.

Biocompatible hypocrellin A-Fe(III) nanoparticles exhibiting efficient photo-activated CDT and .

Chemodynamic therapy (CDT) is novel and promising for cancer treatment, however, the potential systematic toxicity of the used nanoparticles is still a big concern. In this work the biocompatible hypocrellin A-Fe(III) nanoparticles (HA-Fe(III) NPs) were synthesized and studied. The CDT effect of HA-Fe(III) NPs in the dark is negligible but can be photo-activated upon red light irradiation, which is meaningful to realize precise CDT treatment by selective light irradiation.

An Alkynyl-Dangling Ru(II) Polypyridine Complex for Targeted Antimicrobial Photodynamic Therapy.

To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group-containing lipids are rich on the outer surfaces of Gram-positive bacteria, we herein constructed an alkynyl-dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino-yne bio-orthogonal click reaction.

The Development of Ru(II)-Based Photoactivated Chemotherapy Agents.

Photoactivated chemotherapy (PACT) is a novel cancer treatment method that has drawn increasing attention due to its high selectivity and low side effects by spatio-temporal control of irradiation. Compared with photodynamic therapy (PDT), oxygen-independent PACT is more suitable for treating hypoxic tumors. By finely tuning ligand structures and coordination configurations, many Ru(II) complexes can undergo photoinduced ligand dissociation, and the resulting Ru(II) aqua species and/or free ligands may have anticancer activity, showing their potential as PACT agents.

A Ru-anthraquinone dyad with triple functions of PACT, photoredox catalysis and PDT upon red light irradiation.

Phototherapy for cancer treatment has received much attention in recent years, and compounds with multiple anticancer mechanisms upon irradiation are particularly appealing. In this work, a nitro-anthraquinone group was attached to a biq (2,2'-biquinoline) ligand based Ru(ii) complex, endowing the resultant Ru1 compound with multiple anticancer mechanisms upon 600 nm light irradiation. Ru1 can undergo biq ligand photodissociation, showing its potential as a photoactivated chemotherapy (PACT) agent.

Selective and Efficient Photoinactivation of Intracellular and MRSA with Little Accumulation of Drug Resistance: Application of a Ru(II) Complex with Photolabile Ligands.

Novel antibacterial agents capable of efficiently sterilizing intracellular and methicillin-resistant (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex (5 μM) can inhibit more than 90% growth of /MRSA that has invaded in J774A.

UCNP@BSA@Ru nanoparticles with tumor-specific and NIR-triggered efficient PACT activity .

Ru(ii)-based photoactivated chemotherapy (PACT) agents are promising; however, their short wavelength absorption (generally <550 nm) and poor tumor accumulation ability limit their in vivo applications. Herein, bovine serum albumin (BSA) coated lanthanide-doped upconversion nanoparticles (NaYF4:Yb:Tm@NaYF4 (UCNPs)) were loaded with a Ru(ii) PACT agent, i.e.

Photo-induced mitochondrial DNA damage and NADH depletion by -NO modified Ru(II) complexes.

Two mitochondria-localized Ru(ii) complexes with photo-labile ligands were reported to exert one- and two-photon activatable anticancer activity through a dual-function mechanism, i.e. mitochondrial DNA covalent binding after photo-induced ligand dissociation and photo-catalyzed NADH depletion, thus displaying good activity towards cisplatin-resistant cancer cells under both normoxic and hypoxic conditions.

The modification of a pyrene group makes a Ru(ii) complex versatile.

In this work, the simple modification of a pyrene group on the labile ligand gives the resultant complex 1 versatility, for example, "turn-on" fluorescence after photo-dissociation, dual PDT and PACT activity, and a large two-photon absorption cross section.

Polypyridyl Co complex-based water reduction catalysts: why replace a pyridine group with isoquinoline rather than quinoline?

The electronic effect of the substituent has been fully leveraged to improve the activity of molecular water reduction catalysts (WRCs). However, the steric effect of the substituents has received less attention. In this work, a steric hindrance effect was observed in a quinoline-involved polypyridyl Co complex-based water reduction catalyst (WRC), which impedes the formation of Co(iii)-H from Co(i), two pivotal intermediates for H evolution, leading to significantly impaired electrocatalytic and photocatalytic activity with respect to its parent complex, [Co(TPA)Cl]Cl (TPA = tris(2-pyridinylmethyl)-amine).

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands.

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands was studied. Ru(ii) polypyridine complexes containing a di-fluorinated dppz (dipyrido[3,2-:2',3'-]phenazine) or mono-trifluoromethylated dppz bidentate ligand and four pyridine monodentate ligands (complexes 3 and 4) were found to show potent photoactivated antibacterial activity against methicillin-resistant (MRSA), vancomycin-resistant (VRE), and () in both normoxic and hypoxic conditions. The bactericidal effect of complexes 3 and 4 under hypoxic conditions may stem from the fluorine-containing Ru(ii) aqua species after photo-induced pyridine dissociation, and DNA may be the potential antibacterial target.

Chloromethyl-modified Ru(ii) complexes enabling large pH jumps at low concentrations through photoinduced hydrolysis.

Photoacid generators (PAGs) are finding increasing applications in spatial and temporal modulation of biological events and . In these applications, large pH jumps at low PAG concentrations are of great importance to achieve maximal expected manipulation but minimal unwanted interference. To this end, both high photoacid quantum yield and capacity are essential, where the capacity refers to the proton number that a PAG molecule can release.

Smart use of "ping-pong" energy transfer to improve the two-photon photodynamic activity of an Ir(iii) complex.

A two-photon excited "Ping-Pong" type energy transfer process is for the first time disclosed in a pyrene-modified Ir(iii) cyclometalated complex. The energy transfer, from the singlet excited state of the 4-(pyren-1-yl)-tpy (tpy-py) unit to the Ir(iii) moiety and then back again to the triplet excited state of the tpy-py unit, enhances both the two-photon absorption cross sections and singlet oxygen quantum yield of the complex, and dramatically boosts its two-photon photodynamic activity both in vitro and in 3D multicellular spheroids.

Incorporation of 7-dehydrocholesterol into liposomes as a simple, universal and efficient way to enhance anticancer activity by combining PDT and photoactivated chemotherapy.

Cholesterol (CHOL) is an indispensable component of liposomes. Incorporation of 7-dehydrocholesterol (7-DHC) instead of CHOL can efficiently enhance the anticancer activity of photosensitizer-encapsulated liposomes upon irradiation, yielding an IC50 value about half of that of CHOL-based controls. The photo-oxidation of 7-DHC into its endoperoxide form by singlet oxygen may account for the enhanced therapeutic effect, realizing an efficient combination of photodynamic therapy (PDT) and photoactivated chemotherapy.

Selective Photoinactivation of Methicillin-Resistant Staphylococcus aureus by Highly Positively Charged Ru Complexes.

Ruthenium(II) polypyridyl complexes featuring peripheral quaternary ammonium structures were found to be able to selectively inactivate Gram-positive Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA) upon visible light irradiation, but have low phototoxicity toward 293T cells, L02 cells and lack hemolysis toward rabbit red blood cells (RBC), exhibiting promising potential as a novel type of antimicrobial photodynamic therapy (aPDT) agents.

Fluorination on non-photolabile dppz ligands for improving Ru(ii) complex-based photoactivated chemotherapy.

Ru(ii) polypyridine complexes which can undergo photo-induced ligand dissociation and subsequent DNA covalent binding may potentially serve as photoactivated chemotherapeutic (PACT) agents. In this paper, three fluorinated dppz ligand coordinated Ru(ii) complexes (2-4) containing four monodentate pyridine ligands were studied. All complexes released one pyridine and covalently bound to DNA upon 470 nm irradiation.

A nuclear permeable Ru(ii)-based photoactivated chemotherapeutic agent towards a series of cancer cells: in vitro and in vivo studies.

Ru(ii) polypyridyl complexes which can undergo photo-induced ligand dissociation and DNA covalent binding are considered as potential photoactivated chemotherapeutic (PACT) agents. Herein four pyridine-2-sulfonate (py-SO3-) ligand based Ru(ii) complexes [Ru(N-N)2(py-SO3)]+ (1-4) were synthesized and studied. All the complexes can undergo fast py-SO3- ligand dissociation and DNA covalent binding upon visible light irradiation.