Novel Efficient Selenium-Based D-π-A NIR Polymer Dots Anodic Electrochemiluminescence Emitter and Its Application in Simultaneous Detection of Two Pneumonia Pathogens with CdS Quantum Dots.

Community-acquired pneumonia (CAP) is a major cause of death in children under 5 years old globally. With Streptococcus pneumoniae (S. pneumoniae) and Mycoplasma pneumoniae (M. pneumoniae) being the main pathogens linked to CAP that requires hospitalization, there is an urgent need for a straightforward, cost-efficient, and highly accurate diagnostic method for immediate and early detection of CAP. In this work, benzo[1,2-c;4,5-c']bis([1,2,5]thiadiazole) (BBT) as π-bridge spacer with the donor unit of poly(9,9-dioctylfluorene) (PF) and the acceptor unit of dithienylbenzoselenadiazole (DBS) has been successfully copolymerized to unprecedentedly prepare novel D-π-A selenium-based polymer dots with efficient NIR electrochemiluminescence (named as Se-Pdots in this work). Se-Pdots exclusively generated excellent anodic ECL in the two-component coreaction system comprising TPrA and K2S2O8. Moreover, a potential-resolved ECL biosensor to simultaneously detect S. pneumoniae and M. pneumoniae has also been successfully constructed based on this novel Se-based NIR Pdots as an anodic emitter with CdS QDs as a cathodic emitter. Under optimal conditions, the biosensor has a wide linear range for S. pneumoniae (10-15 to 10-9 M) and M. pneumoniae (10-15 to 10-9 M), with low detection limits for S. pneumoniae (0.56 fM) and M. pneumoniae (0.96 fM). The proposed ECL biosensor provides a simple, sensitive, and reliable method for the simultaneous detection of CAP pathogens in clinical applications.

Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia.

Despite the clinical success of photodynamic therapy (PDT), the application of this medical technique is intrinsically limited by the low oxygen concentrations found in cancer tumors, hampering the production of therapeutically necessary singlet oxygen (1O2). To overcome this limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (2-O-IrAn), which, upon two-photon irradiation in NIR, synergistically releases a highly cytotoxic iridium(III) complex (2-IrAn), singlet oxygen, and an alkoxy radical. 2-O-IrAn was found to be highly (photo-)toxic in hypoxic tumor cells and multicellular tumor spheroids (MCTS) in the nanomolar range. To provide cancer selectivity and improve the pharmacological properties of 2-O-IrAn, it was encapsulated into a biotin-functionalized polymer. The generated nanoparticles were found to nearly fully eradicate the tumor inside a mouse model within a single treatment. This study presents, to the best of our knowledge, the first example of an iridium(III)-based endoperoxide prodrug for synergistic photodynamic therapy/photoactivated chemotherapy, opening up new avenues for the treatment of hypoxic tumors.

A Biodegradable Iridium(III) Coordination Polymer for Enhanced Two-Photon Photodynamic Therapy Using an Apoptosis-Ferroptosis Hybrid Pathway.

The clinical application of photodynamic therapy is hindered by the high glutathione concentration, poor cancer-targeting properties, poor drug loading into delivery systems, and an inefficient activation of the cell death machinery in cancer cells. To overcome these limitations, herein, the formulation of a promising IrIII complex into a biodegradable coordination polymer (IrS NPs) is presented. The nanoparticles were found to remain stable under physiological conditions but deplete glutathione and disintegrate into the monomeric metal complexes in the tumor microenvironment, causing an enhanced therapeutic effect. The nanoparticles were found to selectively accumulate in the mitochondria where these trigger cell death by hybrid apoptosis and ferroptosis pathways through the photoinduced production of singlet oxygen and superoxide anion radicals. This study presents the first example of a coordination polymer that can efficiently cause cancer cell death by apoptosis and ferroptosis upon irradiation, providing an innovative approach for cancer therapy.

In situ oxidative polymerization of platinum(iv) prodrugs in pore-confined spaces of CaCO3 nanoparticles for cancer chemoimmunotherapy.

Drug resistance and metastases are the leading causes of death in clinics. To overcome this limitation, there is an urgent need for new therapeutic agents and drug formulations that are able to therapeutically intervene by non-traditional mechanisms. Herein, the physical adsorption and oxidative polymerization of Pt(iv) prodrugs in pore-confined spaces of CaCO3 nanoparticles is presented, and the nanomaterial surface was coated with DSPE-PEG2000-Biotin to improve aqueous solubility and tumor targeting. While the nanoparticle scaffold remained stable in an aqueous solution, it quickly degraded into Ca2+ in the presence of acid and into cisplatin in the presence of GSH. The nanoparticles were found to interact in cisplatin-resistant non-small lung cancer cells by a multimodal mechanism of action involving mitochondrial Ca2+ overload, dual depletion of GSH, nuclear DNA platination, and amplification of ROS and lipid peroxide generation, resulting in triggering cell death by a combination of apoptosis, ferroptosis and immunogenic cell death in vitro and in vivo. This study could present a novel strategy for the treatment of drug-resistant and metastatic tumors and therefore overcome the limitations of currently used therapeutic agents in the clinics.

Nano-assembly of ruthenium(II) photosensitizers for endogenous glutathione depletion and enhanced two-photon photodynamic therapy.

Photodynamic therapy (PDT) is a promising noninvasive cancer treatment. PDT in the clinic faces several hurdles due to the unique tumor environment, a feature of which is high levels of glutathione (GSH). An excess amount of GSH consumes reactive oxygen species (ROS) generated by photosensitizers (PSs), reducing PDT efficiency. Herein, nano-photosensitizers (RuS1 NPs and RuS2 NPs) are reported. These consist of ruthenium complexes joined by disulfide bonds forming GSH sensitive polymer nanoparticles. The NPs achieve enhanced uptake compared to their constituent monomers. Inside cancer cells, high levels of GSH break the S-S bonds releasing PS molecules in the cell. The level of GSH is also then reduced leading to excellent PDT activity. Furthermore, RuS2 NPs functionalized with tumor targeting hyaluronic acid (HA@RuS2 NPs) assessed in vivo were highly effective with minimal side effects. To the best of our knowledge, RuS NPs are the first metal complex-based nano-assembled photosensitizers which exhibit enhanced specificity and consume endogenous GSH simultaneously, thus achieving excellent two-photon PDT efficiency in vitro and in vivo.

Correction: Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy.

Correction for 'Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy' by Libing Ke et al., Chem. Commun., 2019, 55, 10273-10276.

Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy.

Ir(iii) complex modified gold nanorods, Ir@AuNRs, were developed as mitochondria-targeted theranostic nanoagents. Their hypoxia imaging and photothermal therapeutic properties were demonstrated in vitro and in vivo.

Tracking mitochondrial pH fluctuation during cell apoptosis with two-photon phosphorescent iridium(iii) complexes.

Two iridium(iii) complexes with ligands containing morpholine groups were used to track mitochondrial pH fluctuation during cell apoptosis as their emissive intensities linearly increased with increase in pH values.