All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy.

BACKGROUND: Conventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects. RESULTS: Herein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy. CONCLUSIONS: A nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.

Cytological Analysis and Fine Mapping of paa1 (Post-meiosis Abnormal Anther 1) Mutant with Abnormal Tapetum and Microspore Development.

To further understand the molecular mechanism for rice male reproduction, a rice male sterile mutant paa1 was screened from the rice mutant library generated by treatment with 60Coγ-rays. Genetic analysis revealed that paa1 is controlled by a single- recessive nuclear gene, and the anthers of the paa1 mutant were smaller than those of WT plants with a white color. Histological analysis demonstrated that the anthers of the paa1 mutant began to turn abnormal at the microspore stage after meiosis, with abnormal degradation of tapetum, deformed Ubisch bodies, and defective pollen exine. TUNEL assay results also confirmed the delay of tapetum PCD in paa1. Map-based cloning was performed for the PAA1 location. As a result, PAA1 was located in a 88-kb region at the end of chromosome 10, which comprises a total of seven candidate genes, and no genes related to anther development have been reported in this region. The results indicate that PAA1 is an essential gene in regulating tapetum development and pollen/microspore formation after rice meiosis.

Fabrication of emulsion gel based on polymer sanxan and its potential as a sustained-release delivery system for ß-carotene.

Food-grade emulsion gels have attracted increasing attention in food and drug manufacturing, owing to their potential as novel delivery systems for lipophilic bioactive ingredients. Emulsion gels are structurally either a polymeric gel matrix with incorporated emulsion droplets (emulsion-filled gels), or a network of aggregated emulsion droplets (emulsion particulate gels). In this study, a novel emulsion gel was prepared by formulating an oil-in-water (O/W) emulsion stabilized by sanxan alone, followed by heating and cooling treatment, resulting in a structured solid system. Stable O/W type sanxan emulsion gels (SEGs) were obtained at sanxan concentration >0.5% (w/w). Fluorescence microscopy results confirmed the adsorption of sanxan on oil droplet surfaces. The effect of temperature and sanxan/oil concentrations on the rheological and textural properties of the SEGs was evaluated: the SEG containing 1% (w/w) sanxan and 20% (w/w) sunflower oil exhibited excellent rheological and textural properties. Further, the addition of 10 mM Na+ or 5 mM Ca2+ greatly enhanced the thermostability of the SEG. The potential of SEGs as sustained-release delivery systems for ß-carotene was also explored. The findings are of great interest for the development of novel delivery systems based on emulsion gels stabilized by sanxan for the sustained release of lipophilic components.

Manganese threonine chelate-a new enteric contrast agent for MRI: a pilot study on rats.

Enteric contrast agents are important in gastrointestinal MRI. However, no currently available agent is well established as the standard of care. In this study, in vitro relaxivities of manganese threonine chelate (Mn-Thr), a common nutritional food supplement, were measured at 1.5 T and 3 T with further investigation of its efficacy and safety in vivo as an enteric contrast agent. According to the calculated relaxivities, T1 W and T2 W TSE sequences of Mn-Thr solutions at different concentrations were acquired, and the optimal concentration for dark lumen imaging on both T1 W and T2 W images was determined in vitro. To validate the optimal concentration in vivo, eight Sprague-Dawley rats were randomly divided into two groups. Each group received rectal injection of either 2.00 g/L (about 3.80 mM) Mn-Thr or saline as an enteric contrast agent and underwent MRI. After a time interval of one week, the same procedures were repeated with the alternative contrast agent. Animals were sacrificed after the second MRI. Tissue manganese quantification and histopathological examination were obtained. Qualitative MR image quality assessments were performed and compared between Mn-Thr and saline. Measured T1 and T2 relaxivities of Mn-Thr were significantly higher than those of MnCl2 in vitro (p < 0.05). At the concentration of 2.00 g/L (about 3.80 mM), Mn-Thr produced a dark lumen on T1 W and T2 W images both in vitro and in vivo. Compared with saline, Mn-Thr showed significantly more homogenous luminal signal and increased bowel wall conspicuity in image quality assessments. Tissue manganese concentrations were not significantly different between two groups. Histopathological examinations were normal in both groups. Our data suggest that Mn-Thr possesses favorable paramagnetic properties and can create a homogenous dark lumen on T1 W and T2 W images without obvious side effects in healthy rats. As a commercially available nutritional food supplement, Mn-Thr appears to be a promising enteric contrast agent for MRI.

Hydrogen Sulfide Mitigates Myocardial Infarction via Promotion of Mitochondrial Biogenesis-Dependent M2 Polarization of Macrophages.

AIMS: Macrophages are of key importance for tissue repair after myocardial infarction (MI). Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H2S modulates cardiac remodeling and repair post-MI remain to be clarified. RESULTS: In our current study, we showed that H2S supplementation ameliorated pathological remodeling and dysfunction post-MI in wild-type (WT) and CSE KO mice, resulting in decreased infarct size and mortality, accompanied by an increase in the number of M2-polarized macrophages at the early stage of MI. Strikingly, adoptive transfer of NaHS-treated bone marrow-derived macrophages into WT and CSE KO mice with depleted macrophages also ameliorated MI-induced cardiac functional deterioration. Further mechanistic studies demonstrated that NaHS-induced M2 polarization was achieved by enhanced mitochondrial biogenesis and fatty acid oxidation. INNOVATION AND CONCLUSION: Our study shows (for the first time) that H2S may have the potential as a therapeutic agent for MI via promotion of M2 macrophage polarization. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16:293-296, 2012) with the following serving as open reviewers: Hideo Kimura, Chaoshu Tang, Xiaoli Tian, and Kenneth Olson. Antioxid. Redox Signal. 25, 268-281.