Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles.

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.

Codelivery of π-π Stacked Dual Anticancer Drugs Based on Aloe-Derived Nanovesicles for Breast Cancer Therapy.

To overcome the low efficacy of conventional monotherapeutic approaches that use a single drug, functional nanocarriers loaded with an amalgamation of anticancer drugs have been promising in cancer therapy. Herein, aloe-derived nanovesicles (gADNVs) are modified with an active integrin-targeted peptide (Arg-Gly-Asp, RGD) by the postinsertion technique to deliver indocyanine green (ICG) and doxorubicin (DOX) for efficient breast cancer therapy. We presented for the first time that the π-π stacking interaction can turn the "competitive" relationship of ICG and DOX inside gADNVs into a "cooperative" relationship and enhance their loading efficiency. The dual-drug codelivery nanosystem, denoted as DIARs, was well stable and leakproof, exhibiting high tumor-targeting capability both in vitro and in vivo. Meanwhile, this nanosystem showed significant inhibition of cell growth and migration and induced cell apoptosis with the combination of phototherapy and chemotherapy. Intravenous administration of DIARs exhibited high therapeutic efficacy in a 4T1 tumor-bearing mouse model and exhibited no obvious damage to other organs. Overall, our DIAR nanosystem constitutively integrated the natural and economical gADNVs, π-π stacking interaction based on efficient drug loading, and tumor-targeted RGD modification to achieve an effective combination therapy for breast cancer.

Yishen Huazhuo Decoction Induces Autophagy to Promote the Clearance of Aß1-42 in SAMP8 Mice: Mechanism Research of a Traditional Chinese Formula Against Alzheimer's Disease.

BACKGROUND: Studies have found that autophagy could promote the clearance of Aß. To promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. OBJECTIVE: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. METHODS: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl's staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aß, LAMP1, and autophagy related proteins. RESULTS: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD group increased significantly (P=0.02<0.05). Nissl's staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group that the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aß1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. CONCLUSION: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aß1-42 to improve memory impairment in SAMP8 mice.

Radix Hedysari polysaccharide suppresses lipid metabolism dysfunction in a rat model of non­alcoholic fatty liver disease via adenosine monophosphate­activated protein kinase pathway activation.

Oxidative stress and excess hepatic lipid accumulation contribute to non­alcoholic fatty liver disease. Radix Hedysari polysaccharides (RHP) have attracted interest due to their antioxidant properties and immunomodulatory effects. However, the effect of RHP on hepatic lipid metabolism remains to be elucidated. In the present study, the response of Sprague­Dawley rat livers to a high­fat diet and RHP treatment was investigated by evaluating body weight, liver histology, hepatic lipid content, adenosine monophosphate­activated protein kinase (AMPK) activity and lipid metabolism gene transcriptional profiles. The present study demonstrated that RHP ameliorated lipid metabolism disorders, regulated hepatic lipid content, improved liver inflammation and damage, activated AMPK via phosphorylation, upregulated peroxisome proliferator­activated receptor α and downregulated the mRNA expression of sterol regulatory element binding protein­1c in rat livers, which reduced lipogenesis and increased lipolysis. Taken together, these results suggested that RHP effectively ameliorates lipid metabolism disorders in rat livers; thus, RHP may be a potential therapeutic agent in the prevention of hepatic steatosis.

[Influence of decomposition of Cladophora sp. on phosphorus concentrations and forms in the overlying water].

Sediments were sampled in the dominated zone of Cladophora sp. in Rongcheng Swan Lake, and cultivated with algae in the laboratory to reveal the influence of Cladophora decomposition on concentrations and forms of phosphorus in the overlying water. Concentrations of total phosphorus (TP), dissolved total phosphorus (DTP), soluble reactive phosphorus (SRP), particulate phosphorus (PP) and dissolved organic phosphorus (DOP) in overlying water were investigated, and some physicochemical parameters, such as dissolved oxygen (DO), pH and conductivity were monitored during the experiment. In addition, the influence of algae decomposition on P release from sediments was analyzed. Due to the decomposition of Cladophora, DO concentration in the overlying water declined remarkably and reached the anoxic condition (0-0.17 mg x L(-1)). The pH value of different treatments also decreased, and treatments with algae reduced by about 1 unit. Concentrations of TP and different P forms all increased obviously, and the increasing extent was larger with the adding algae amount. TP concentrations of different treatments varied from 0.04 mg x L(-1) to 1.34 mg x L(-1). DOP and PP were the main P forms in the overlying water in algae without sediments treatments, but SRP concentrations became much higher in algae with sediments treatments. The result showed that P forms released from decomposing Cladophora were mainly DOP and PP, and the Cladophora decomposition could also promote the sediments to release P into the overlying water.