A core-shell structure QRu-PLGA-RES-DS NP nanocomposite with photothermal response-induced M2 macrophage polarization for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a degenerative joint disease caused by autoimmunity; for the effective treatment of RA while avoiding the side effects of conventional drugs, we have proposed a new therapeutic strategy to eliminate the inflammatory response in RA by regulating the immune system that promotes the transformation of M1-type macrophages to M2-type macrophages. Herein, we designed and synthesized a core-shell nanocomposite (QRu-PLGA-RES-DS NPs), which showed an effective therapeutic effect on RA by accurately inducing the polarization of M2 macrophages. In this system, the quadrilateral ruthenium nanoparticles (QRuNPs) with a photothermal effect were utilized as a core and the thermosensitive molecular poly (lactic-co-glycolic acid) (PLGA) modified with the targeted molecule dextran sulfate (DS) was employed as a shell. Then, the nanocarrier QRu-PLGA-DS NPs effectively improved the water solubility and targeting of resveratrol (RES) through self-assembly. Therefore, the QRu-PLGA-RES-DS NPs significantly enhanced the ability of RES to reverse the M1 type macrophages to the M2 type macrophages through an accurate release. In vivo experiments further demonstrated that the QRu-PLGA-RES-DS NPs could effectively accumulate in the lesion area with an exogenous stimulus, and this significantly enhanced the transformation of the M2 type macrophages and decreased the recruitment of the M1 type macrophages. Furthermore, the QRu-PLGA-RES-DS NPs effectively treated RA by eliminating the inflammatory response; in addition, photoacoustic imaging (PA) of the QRu NPs provided image guidance for the distribution and analysis of nanomedicine in inflammatory tissues. Hence, this therapeutic strategy promotes the biological applications of Ru-based nanoparticles in disease treatment.

Flexible Modulation of CO-Release Using Various Nuclearity of Metal Carbonyl Clusters on Graphene Oxide for Stroke Remediation.

Utilizing the size-dependent adsorption properties of ruthenium carbonyl clusters (Ru-carbon monoxide (CO)) onto graphene oxide (GO), a facile CO-release platform for in situ vasodilation as a treatment for stroke-related vascular diseases is developed. The rate and amount of formation of the CO-release-active RuII (CO)2 species can be modulated by a simple mixing procedure at room temperature. The subsequent thermally induced oxidation of RuII (CO)2 to RuO2 on the GO surface results in the release of CO. Further modulation of thermal and CO-release properties can be achieved via a hybridization of medium- and high-nuclearity of Ru-CO clusters that produces a RuO2 /RuII (CO)2 /6 Ru-CO-GO composite, where 6 Ru-CO-GO provides a photothermally activated reservoir of RuII (CO)2 species and the combined infrared absorption properties of GO and RuO2 provides photothermal response for in situ CO-release. The RuO2 /RuII (CO)2 /6 Ru-CO-GO composite does not produce any cytotoxicity and the efficacy of the composite is further demonstrated in a cortical photothrombotic ischemia rat model.

Long Blood Residence and Large Tumor Uptake of Ruthenium Sulfide Nanoclusters for Highly Efficient Cancer Photothermal Therapy.

Transition metal sulfide (TMS) holds great potential in cancer photothermal therapy (PTT) because of the high absorbance in the near-infrared (NIR) region. The short blood circulation time and limited tumor accumulation of TMS-based photothermal agents, however, limit their applications. Herein, we design a novel TMS-based PTT agent, ruthenium sulfide-based nanoclusters (NCs), to overcome the current limitations. We firstly develop a simple method to prepare oleic acid coated ruthenium sulfide nanodots (OA-RuS1.7 NDs) and assemble them into water-soluble NCs via sequentially coating with denatured bovine serum albumin (dBSA) and poly(ethylene glycol) (PEG). The obtained PEG-dBSA-RuS1.7 NCs possess excellent photothermal conversion ability. More significantly, they exhibit enhanced blood circulation time and tumor-targeting efficiency in vivo compared with other TMS-based PTT nanoagents, which may be attributed to their appropriate hydrodynamic diameter (~70 nm) and an ideal charge (~0 mV). These characteristics help the PEG-dBSA-RuS1.7 NCs to escape the removal by the reticuloendothelial system (RES) and kidney. All these advantages enable the PEG-dBSA-RuS1.7 NCs to selectively concentrate in tumor sites and effectively ablate the cancer cells upon NIR irradiation.

The water soluble ruthenium(II) organometallic compound [Ru(p-cymene)(bis(3,5 dimethylpyrazol-1-yl)methane)Cl]Cl suppresses triple negative breast cancer growth by inhibiting tumor infiltration of regulatory T cells.

Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favorable toxicity and clearance properties. Here, we show that the ruthenium(II) complex [Ru(p-cymene)(bis(3,5-dimethylpyrazol-1-yl)methane)Cl]Cl (UNICAM-1) exhibits potent in vivo antitumor effects. When administered as four-dose course, by repeating a single dose (52.4mgkg-1) every three days, UNICAM-1 significantly reduces the growth of A17 triple negative breast cancer cells transplanted into FVB syngeneic mice. Pharmacokinetic studies indicate that UNICAM-1 is rapidly eliminated from kidney, liver and bloodstream thanks to its high hydrosolubility, exerting excellent therapeutic activity with minimal side effects. Immunohistological analysis revealed that the efficacy of UNICAM-1, mainly relies on its capacity to reverse tumor-associated immune suppression by significantly reducing the number of tumor-infiltrating regulatory T cells. Therefore, UNICAM-1 appears very promising for the treatment of TNBC.