Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

A Novel Targeted and High-Efficiency Nanosystem for Combinational Therapy for Alzheimer's Disease.

Alzheimer's disease (AD) remains the most prevalent neurodegenerative disease, and no effective treatment is available yet. Metal-ion-triggered aggregates of amyloid-beta (Aß) peptide and acetylcholine imbalance are reported to be possible factors in AD pathogenesis. Thus, a combination therapy that can not only inhibit and reduce Aß aggregation but also simultaneously regulate acetylcholine imbalance that can serve as a potential treatment for AD is needed. Here, clioquinol (metal-ion chelating agent) and donepezil (acetylcholinesterase (AChE) inhibitor) co-encapsulated human serum albumin (HSA) nanoparticles (dcHGT NPs) are designed, which are modified with transcriptional activator protein (TAT) and monosialotetrahexosylganglioside (GM1). The GM1 lipid and TAT peptide endow this drug delivery nanosystem with high brain entry efficiency and long-term retention capabilities through intranasal administration. It is found that dcHGT NPs can significantly inhibit and eliminate Aß aggregation, relieve acetylcholine-related inflammation in microglial cells, and protect primary neurons from Aß oligomer-induced neurotoxicity in vitro. The alleviation of Aß-related inflammation and AChE-inhibited effect further synergistically adjust acetylcholine imbalance. It is further demonstrated that dcHGT NPs reduce Aß deposition, ameliorate neuron morphological changes, rescue memory deficits, and greatly improve acetylcholine regulation ability in vivo. This multifunctional synergetic nanosystem can be a new candidate to achieve highly efficient combination therapy for AD.

Correction: An NIR-responsive mesoporous silica nanosystem for synergetic photothermal-immunoenhancement therapy of hepatocellular carcinoma.

Correction for 'An NIR-responsive mesoporous silica nanosystem for synergetic photothermal-immunoenhancement therapy of hepatocellular carcinoma' by Han Yang et al., J. Mater. Chem. B, 2020, 8, 251-259.

An NIR-responsive mesoporous silica nanosystem for synergetic photothermal-immunoenhancement therapy of hepatocellular carcinoma.

To create a more precise, efficient imaging and therapeutic strategy is a big challenge for the current treatment of hepatocellular carcinoma (HCC). Photothermal therapy (PTT) has attracted enormous attention due to its non-invasive property and precise spatial and temporal control. Here, we developed a strategy to realize superior imaging performance and treatment, utilizing an indocyanine green (ICG) and sorafenib (S) co-loaded mesoporous silica nanosystem for synergetic PTT/immuno-enhanced therapy. We proved that (ICG+S)@mSiO2 could be easily endocytosed by H22 cells, carried out outstanding real-time fluorescence imaging, and enhanced cytotoxicity abilities by near-infrared radiation (NIR) in vitro. Moreover, (ICG+S)@mSiO2 also had excellent fluorescence imaging ability, displayed a remarkable photothermal tumor killing effect and immune enhancement capability under 808 nm irradiation in an H22 tumor-bearing mice model, without apparent adverse effects in other organs. This study provides a new strategy for the development of a PTT/immuno-enhanced synergistic theranostic nanosystem of HCC.

Construction of ICG encapsulated W18O49@MSN as a fluorescence carrier for real-time tracked photothermal therapy.

Photothermal therapy (PTT) has drawn tremendous attention because of its high therapeutic efficiency in targeting cells while minimizing the damage to normal tissues and organs. Tungsten oxide (W18O49, WO) plays a pivotal role in PTT development and its use in PTT systems has been extensively studied. However, it is difficult to control morphology of WO through conventional hydrothermal method. Which make its related researches have been limited up to now. In this study, we describe the construction and effects on tumor of a novel nanoplatform based on WO and indocyanine green (ICG) loaded in mesoporous silica nanoparticles (MSN) for dual-modal PTT and near-infrared imaging. (WO+ICG)@MSN could efficiently control WO shape without the need of surface modification due to its water-soluble of MSN. (WO+ICG)@MSN produced a PTT synergistic effect under irradiation of a single 808nm near-infrared (NIR) laser. Notably, an enhanced lethal effect of the 808nm laser triggering dual-modal therapy on B16 tumor cells was observed. The in vivo animal experiments showed that (WO+ICG)@MSN induced an effective solid tumor reduction under 808nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR-mediated dual-modal therapeutic platform for cancer treatment.

New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine-A-loaded PLGA/polymeric liposomes.

Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over ∼25 h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP-43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso-Beattie-Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4 h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI.

Persistent Luminescent Nanocarrier as an Accurate Tracker in Vivo for Near Infrared-Remote Selectively Triggered Photothermal Therapy.

Optical imaging-guidance of indocyanine green (ICG) for photothermal therapy (PTT) has great latent capacity in cancer therapy. However, the conventional optical image-guidance mode has caused strong tissue autofluorescence of the living tissue, which leads to the accurate infrared light irradiation cannot be conducted. In this article, ICG and persistent luminescence phosphors (PLPs) coloaded mesoporous silica nanocarriers ((ICG+PLPs)@mSiO2) were first designed and prepared for persistent luminescent imaging-guided PTT. The (ICG+PLPs)@mSiO2 nanocarriers could significantly improve signal-to-noise ratio during luminescence imaging-guided PTT, making the PLP promising for improving the accuracy of the tumor site for photothermal therapy in vivo. This paper is likely to develop a new way for accurately regulating cancer cell death based on luminescence imaging-guided PTT selectively triggered by near-infrared (NIR)-remote.

[Study of TAT-PEG loaded magnetic liposomes crossing blood spinal cord barrier after spinal cord injury in rats].

OBJECTIVE: To evaluate the ability of a kind of novel magnetic liposomes modified with polyethylene glycol (PEG) and transactivating-transduction protein (TAT) to cross the blood spinal cord barrier (BSCB) so as to demonstrate whether or not they can accumulate at the lesions of injured spinal cord. METHODS: The novel liposomes were made through reverse-phase evaporation method modified with polyethylene glycol (PEG) and transactivating-transduction protein (TAT) with an iron core. Thirty-six Wistar rats subject to spinal cord injury (SCI) at T10 were randomly divided into three groups (Groups I, II and III). The rats of Group III were injected with TAT-PEG loaded magnetic liposomes (4.55 mg/kg). The rats of GroupII received an injection of the equivalent PEG loaded magnetic liposomes while those of control group (GroupI) the equivalent normal saline. The accumulation of liposomes was observed by MRI (magnetic resonance imaging), Prussian blue staining, electron microscope and flame atomic absorption spectrophotometer. RESULTS: This kind of TAT-PEG loaded magnetic liposomes could cross the BSCB and enter into the cells around the injured tissue. A low signal of T2WI on MRI could also be found in Group III. The results of flame atomic absorption spectrophotometer showed that the iron content accumulated around the lesion site in Group III was obviously higher than the other two groups (P < 0.05). CONCLUSION: The TAT-PEG loaded magnetic liposomes may be employed as one kind of novel drug carrier to cross the BSCB and accumulate at tissue cells of spinal cord. It is likely to become a new therapy for SCI.

Novel multifunctional polyethylene glycol-transactivating-transduction protein-modified liposomes cross the blood-spinal cord barrier after spinal cord injury.

The blood-spinal cord barrier (BSCB) prevents many macromolecular agents from passing through to reach sites of injury in the spinal cord. This study evaluated the ability of a novel multifunctional liposome modified with polyethylene glycol (PEG) and transactivating-transduction protein (TAT) containing an iron core to cross the BSCB using a rat model of spinal cord injury. Rats were examined daily for a period of three days after spinal cord injury and injection of either the multifunctional modified liposome or control formulations using a 3.0 T magnetic resonance imaging spectrometer. A low signal was observed in the T2-weighted images. Prussian blue staining and flame atomic absorption spectrophotometry revealed that significantly more iron accumulated around the lesion site in the experimental group than the control groups (P < 0.05). The findings from this study suggest that this multifunctional liposome carrier can cross the BSCB to accumulate around the lesion site.

A field experimental study of lignin sand stabilizing material (LSSM) extracted from spent-liquor of straw pulping paper mills.

A new technique was introduced for sand stabilization and re-vegetation by use of lignin sand stabilizing material (LSSM). LSSM is a reconstructed organic compound with lignin as the most dominant component from the extracts of black-liquor issued by straw pulp paper mills. Unlike the polyvinyl acetate or foamed asphalt commonly used for dune stabilization, the new material is plant-friendly and can be used with virescence actions simultaneously. The field experimental study was conducted since 2001 in China's Northwest Ningxia Hui Autonomous Region and has been proved that LSSM is effective in stabilizing the fugitive dunes, making the arenaceous plants survive and the bare dune vegetative. The advisable solution concentration is 2% and the optimal field spraying quantity is 2.5 L/m2. The soil nutrients of the stabilized and greened dune, such as organic matter, available phosphorous and total nitrogen are all increased compared with the control treatment, which is certainly helpful to the growth of arenaceous plants. The technique is worthwhile to be popularized because it is provided not only a new method for desertification control but also an outlet for cleaning contaminants issued from the straw paper mills.