Correction to "Shifting the Antibody-Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model".

[This corrects the article DOI: 10.1021/acsptsci.3c00270.

Shifting the Antibody-Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model.

Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutics to target cancers without toxicity to normal tissue. Clinically, most chemotherapeutic ADCs are based on complex organic molecules, while the conjugation of metallodrugs to mAbs has been overlooked, despite the resurgent interest in metal-based drugs as cancer chemotherapeutics. In 2019, we described the first gold ADCs containing gold-triphenylphosphane fragments as a proof of concept.

From Chemotherapy to Phototherapy - Changing the Therapeutic Action of a Metallo-Intercalating Ru -Re Luminescent System by Switching its Sub-Cellular Location.

The synthesis of a new heterodinuclear Re Ru metallointercalator containing Ru (dppz) and Re (dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent.

Synthesis and Characterization of Lipophilic Salts of Metformin to Improve Its Repurposing for Cancer Therapy.

Epidemiological evidence has accentuated the repurposing of metformin hydrochloride for cancer treatment. However, the extreme hydrophilicity and poor permeability of metformin hydrochloride are responsible for its poor anticancer activity and . Here, we report the synthesis and characterization of several lipophilic metformin salts containing bulky anionic permeation enhancers such as caprate, laurate, oleate, cholate, and docusate as counterions.

Photoactive metal complexes that bind DNA and other biomolecules as cell probes, therapeutics, and theranostics.

This review discusses the advantages of using luminescent d-transition-metal complexes as cell probes for optical microscopy. In particular it focusses on the Thomas group's use of specific complexes as "building blocks" toward the construction of biomolecular binding substrates, with DNA being a particular target. Using this approach, a range of new imaging probes for conventional optical microscopy, nanoscopy and transmission electron microscopy have been identified.

Making the Right Link to Theranostics: The Photophysical and Biological Properties of Dinuclear Ru-Re dppz Complexes Depend on Their Tether.

The synthesis of new dinuclear complexes containing linked Ru(dppz) and Re(dppz) moieties is reported. The photophysical and biological properties of the new complex, which incorporates a ,'-bis(4-pyridylmethyl)-1,6-hexanediamine tether ligand, are compared to a previously reported Ru/Re complex linked by a simple dipyridyl alkane ligand. Although both complexes bind to DNA with similar affinities, steady-state and time-resolved photophysical studies reveal that the nature of the linker affects the excited state dynamics of the complexes and their DNA photocleavage properties.

Exploring the Cytotoxicity, Uptake, Cellular Response, and Proteomics of Mono- and Dinuclear DNA Light-Switch Complexes.

Drug resistance to platinum chemotherapeutics targeting DNA often involves abrogation of apoptosis and has emerged as a significant challenge in modern, non-targeted chemotherapy. Consequently, there is great interest in the anti-cancer properties of metal complexes-particularly those that interact with DNA-and mechanisms of consequent cell death. Herein we compare a parent cytotoxic complex, [Ru(phen)(tpphz)] [phen = 1,10-phenanthroline, tpphz = tetrapyridyl[3,2- a:2',3'- c:3″,2″- h:2‴,3‴- j]phenazine], with a mononuclear analogue with a modified intercalating ligand, [Ru(phen)(taptp)] [taptp = 4,5,9,18-tetraazaphenanthreno[9,10- b] triphenylene], and two structurally related dinuclear, tpphz-bridged, heterometallic complexes, RuRe and RuPt.

A three-in-one-bullet for oesophageal cancer: replication fork collapse, spindle attachment failure and enhanced radiosensitivity generated by a ruthenium(ii) metallo-intercalator.

Substitutionally inert ruthenium(ii) polypyridyl complexes have been developed as DNA intercalating agents yet cellular DNA damage responses to this binding modality are largely unexplored. Here, we show the nuclear-targeting complex [Ru(phen)(tpphz)] (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) generates rapid and pronounced stalling of replication fork progression in p53-deficient human oesophageal cancer cells. In response, replication stress and double-strand break (DSB) DNA damage response (DDR) pathways are activated and cell proliferation is inhibited by growth arrest.

Tracking HOCl concentrations across cellular organelles in real time using a super resolution microscopy probe.

BODIPY derivative, SF-1, exclusively shows a fluorescence ON response to HOCl and images endogenously generated HOCl in RAW 264.7 macrophages. Widefield and super resolution structured illumination microscopy images confirm localization in the Golgi complex and lysosomes, and hence specifically detects HOCl generated in these organelles.

A Super-Resolution Probe To Monitor HNO Levels in the Endoplasmic Reticulum of Cells.

Selective detection of nitroxyl (HNO), which has recently been identified as a reactive nitrogen species, is a challenging task. We report a BODIPY-based luminescence ON reagent for detection of HNO in aqueous solution and in live RAW 264.7 cells, based on the soft nucleophilicity of the phosphine oxide functionality toward HNO.

Multimodal Super-resolution Optical Microscopy Using a Transition-Metal-Based Probe Provides Unprecedented Capabilities for Imaging Both Nuclear Chromatin and Mitochondria.

Detailed studies on the live cell uptake properties of a dinuclear membrane-permeable Ru cell probe show that, at low concentrations, the complex localizes and images mitochondria. At concentrations above ∼20 μM, the complex images nuclear DNA. Because the complex is extremely photostable, has a large Stokes shift, and displays intrinsic subcellular targeting, its compatibility with super-resolution techniques was investigated.

Homo- and Heteroleptic Phototoxic Dinuclear Metallo-Intercalators Based on Ru (dppn) Intercalating Moieties: Synthesis, Optical, and Biological Studies.

Using a new mononuclear "building block," for the first time, a dinuclear Ru (dppn) complex and a heteroleptic system containing both Ru (dppz) and Ru (dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are O sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence "switch on" DNA light-switch effect.

The Structure of Linkers Affects the DNA Binding Properties of Tethered Dinuclear Ruthenium(II) Metallo-Intercalators.

With the long-term aim of enhancing the binding properties of dinuclear Ru -based DNA light-switch complexes, a series of eight structurally related mono- and dinuclear systems are reported in which the linker of the bridging ligand has been modulated. These tethered systems have been designed to explore issues of steric demand at the binding site and the thermodynamic cost of entropy loss upon binding. Detailed spectroscopic and isothermal titration calorimetry (ITC) studies on the new complexes reveal that one of the linkers produces a dinuclear system that binds to duplex DNA with an affinity (K >10  m ) that is higher than its corresponding monometallic complex and is the highest affinity for a non-threading bis-intercalating metal complex.