Kangqiang Qiu

Noncovalent Ruthenium(II) Complexes–Single-Walled Carbon Nanotube Composites for Bimodal Photothermal and Photodynamic Therapy with Near-Infrared Irradiation

To enhance the efficacy and optimize the treatment of cancers, the integration of multimodal treatment strategies leading to synergistic effects is a promising approach. The coassembly of multifunctional agents for systematic therapies has received considerable interest in cancer treatment. Herein, Ru(II) complex-functionalized single-walled carbon nanotubes (Ru@SWCNTs) are developed as nanotemplates for bimodal photothermal and two-photon photodynamic therapy (PTT-TPPDT). SWCNTs have the ability to load a great amount of Ru(II) complexes (Ru1 or Ru2) via noncovalent π-π interactions. The loaded Ru(II) complexes are efficiently released by the photothermal effect of irradiation from an 808 nm diode laser (0.25 W/cm(2)). The released Ru(II) complexes produce singlet oxygen species ((1)O2) upon two-photon laser irradiation (808 nm, 0.25 W/cm(2)) and can be used as a two-photon photodynamic therapy (TPPDT) agent. Based on the combination of photothermal therapy and two-photon photodynamic therapy, Ru@SWCNTs have greater anticancer efficacies than either PDT using Ru(II) complexes or PTT using SWCNTs in two-dimensional (2D) cancer cell and three-dimensional (3D) multicellular tumor spheroid (MCTS) models. Furthermore, in vivo tumor ablation is achieved with excellent treatment efficacy under a diode laser (808 nm) irradiation at the power density of 0.25 W/cm(2) for 5 min. This study examines an efficacious bimodal PTT and TPPDT nanoplat form for the development of cancer therapeutics.

Long-Term Lysosomes Tracking with a Water-Soluble Two-Photon Phosphorescent Iridium(III) Complex.

Lysosomes are the stomachs of the cells that degrade endocytosis and intracellular biomacromolecules and participate in various other cellular processes, such as apoptosis and cell migration. The ability of long-term tracking of lysosomes is very important to understand the details of lysosomal functions and to evaluate drug and gene delivery systems. For studying lysosomes, we designed and synthesized a water-soluble triscyclometalated iridium(III) complex (Ir-lyso) attaching morpholine moieties. The phosphorescent intensity of Ir-lyso is responsive to pH and decreases with an increase in the pH but not quenching in high pH. With excellent two-photon properties, Ir-lyso was used to light up the lysosomes in living cells and 3D tumor spheroids. Moreover, Ir-lyso could label lysosomes more than 4 days, so we developed this complex to act as a long-term probe for tracking lysosomes during cell migration and apoptosis. To the best of our knowledge, this is the first paradigm of metal complexes as the two-photon phosphorescent probe for long-term lysosomes tracking.

Real-time tracking mitochondrial dynamic remodeling with two-photon phosphorescent iridium (III) complexes.

Mitochondrial fission and fusion control the shape, size, number, and function of mitochondria in the cells of organisms from yeast to mammals. The disruption of mitochondrial fission and fusion is involved in severe human diseases such as Parkinsons disease, Alzheimers disease, metabolic diseases, and cancers. Agents that can real-time track the mitochondrial dynamics are of great importance. However, the short excitation wavelengths and rapidly photo-bleaching properties of commercial mitochondrial dyes render them unsuitable for tracking mitochondrial dynamics. Thus, mitochondrial targeting agents that exhibit superior photo-stability under continual light irradiation, deep tissue penetration and at intrinsically high three-dimensional resolutions are urgently needed. Two-photon-excited compounds employ low-energy near-infrared light and have emerged as a non-invasive tool for real-time cell imaging. Here, cyclometalated Ir(III) complexes (Ir1-Ir5) are demonstrated as one- and two-photon phosphorescent probes for the real-time imaging and tracking of mitochondrial fission and fusion. The results indicate that Ir2 is well suited for two-photon phosphorescent tracking of mitochondrial fission and fusion in living cells and in Caenorhabditis elegans (C. elegans). This study provides a practical use for mitochondrial targeting two-photon phosphorescent Ir(III) complexes.

Biscylometalated iridium(III) complexes target mitochondria or lysosomes by regulating the lipophilicity of the main ligands

An efficient method was developed that controls biscylometalated iridium(iii) complexes to target mitochondria or lysosomes by regulating the lipophilicity of the main ligands.

Mitochondria-specific imaging and tracking in living cells with two-photon phosphorescent iridium(III) complexes

Two-photon phosphorescent probes have emerged as promising molecular tools for imaging subcellular organelles. Here, the facile synthesis of four new iridium(iii)-based mitochondrial probes with two-photon phosphorescence, Ir1-Ir4, is presented. Ir1-Ir4 possess high specificity for mitochondrial localization, which is advantageous in comparison with commercially available mitochondrial trackers of changes in the mitochondrial membrane potential in live cells. In addition to low cytotoxicity and high resistance to photobleaching, Ir1-Ir4 are applicable for imaging and tracking of mitochondrial morphological changes during the early stages of apoptosis. While naturally possessing intensive two-photon properties, Ir1-Ir4 were further developed for imaging of the mitochondria in 3D multicellular spheroids.

Lipophilic Tetranuclear Ruthenium(II) Complexes as Two‐Photon Luminescent Tracking Non‐Viral Gene Vectors

Fluorescence detection is the most effective tool for tracking gene delivery in living cells. To reduce photodamage and autofluorescence and to increase deep penetration into cells, choosing appropriate fluorophores that are capable of two-photon activation under irradiation in the NIR or IR regions is an effective approach. In this work, we have developed six tetranuclear ruthenium(II) complexes, GV1-6, and have studied their one- and two-photon luminescence properties. DNA interaction studies have demonstrated that GV2-6, bearing hydrophobic alkyl ether chains, show more efficient DNA condensing ability but lower DNA binding constants than GV1. However, the hydrophobic alkyl ether chains also enhance the DNA delivery ability of GV2-6 compared with that of GV1. More importantly, we have applied GV1-6 as non-viral gene vectors for tracking DNA delivery in living cells by one- and two-photon fluorescence microscopies. In two-photon microscopy, a high signal-to-noise contrast was achieved by irradiation with an 830 nm laser. This is the first example of the use of transition-metal complexes for two-photon luminescent tracking of the cellular pathways of gene delivery and as DNA carriers. Our work provides new insights into improving real-time tracking during gene delivery and transfection as well as important information for the design of multifunctional non-viral vectors.

A dendritic nano-sized hexanuclear ruthenium(II) complex as a one- and two-photon luminescent tracking non-viral gene vector

Fluorescent tracking gene delivery could provide us with a better understanding of the critical steps in the transfection process. However, for in vivo tracking applications, a small diameter (<10 nm) is one of the rigorous requirements for tracking vectors. Herein, we have demonstrated a new paradigm for two-photon tracking gene delivery based on a dendritic nano-sized hexanuclear ruthenium(II) polypyridyl complex. Because this metallodendrimer has a multivalent periphery, the complex, which is 6.1 nm, showed high stability and excellent dispersibility and could stepwise condense DNA in vitro. With the outstanding photochemical properties of Ru(II) polypyridyl, this complex could track gene delivery in vivo using one- and two-photon imaging.

Mitochondrial Dynamics Tracking with Two-Photon Phosphorescent Terpyridyl Iridium(III) Complexes

Mitochondrial dynamics, including fission and fusion, control the morphology and function of mitochondria, and disruption of mitochondrial dynamics leads to Parkinson’s disease, Alzheimer’s disease, metabolic diseases, and cancers. Currently, many types of commercial mitochondria probes are available, but high excitation energy and low photo-stability render them unsuitable for tracking mitochondrial dynamics in living cells. Therefore, mitochondrial targeting agents that exhibit superior anti-photo-bleaching ability, deep tissue penetration and intrinsically high three-dimensional resolutions are urgently needed. Two-photon-excited compounds that use low-energy near-infrared excitation lasers have emerged as non-invasive tools for cell imaging. In this work, terpyridyl cyclometalated Ir(III) complexes (Ir1-Ir3) are demonstrated as one- and two-photon phosphorescent probes for real-time imaging and tracking of mitochondrial morphology changes in living cells.

Tetranuclear ruthenium(II) complexes with oligo-oxyethylene linkers as one- and two-photon luminescent tracking non-viral gene vectors

To prolong the observation time, increase the penetration depth and decrease self-absorption and phototoxicity, two-photon luminescent vectors have emerged as promising tools for tracking gene delivery in living cells. Herein, we report four new tetranuclear Ru(ii) complexes based on oligo-oxyethylene and polybenzimidazole as one- and two- photon luminescent tracking non-viral gene vectors. In such a molecular design, the oligo-oxyethylene, polybenzimidazole and Ru(ii) polypyridyl complexes were expected to render the vectors with increased cell permeability, biocompatibility, proton buffering capacity and one- and two-photon luminescence. Corresponding DNA interaction studies showed that the ability of the complexes to condense DNA decreased with increasing oligo-oxyethylene lengths. Additionally, all complexes protected DNA. The complexes were investigated as one- and two-photon tracking non-viral gene vectors in living cells and showed proper cellular uptake, good luciferase expression and low cytotoxicity.

Two-photon photodynamic ablation of tumor cells by mitochondria-targeted iridium(III) complexes in aggregate states

By integrating targeting, imaging and treatment, organelle-targeted photodynamic therapy (PDT) has been reported to be an effective strategy for cancer therapy. However, targeting leads to the accumulation of photosensitizers (PSs) in the targeted organelles, which leads to a reduction in 1O2 generation and fluorescence quenching, especially for the lipophilic mitochondria-targeted PSs. Moreover, because PSs always need exposure to light for a specific period, photobleaching is difficult to avoid. To address these issues, two iridium(iii) complexes with aggregation-induced two-photon emission (AITPE) characteristics were developed. With lipophilicity, the complexes aggregated in water and targeted mitochondria. Owing to their impressive 1O2 production quantum yields and excellent two-photon properties in the aggregate states, the complexes were successfully used for mitochondria-targeted two-photon PDT in monolayer cells and multicellular spheroids. Our results highlighted that the use of a PS with aggregation enhanced 1O2 generation and fluorescence is an effective solution for aggregation in organelle-targeted PDT.