A New Gold Nanoparticles and Paclitaxel Co-Delivery System for Enhanced Anti-Cancer Effect Through Chemo-Photothermal Combination.

Limited chemotherapeutic efficiency, drug resistance and side effect are primary obstacles for cancer treatment. The development of co-delivery system with synergistic treatment modes should be a promising strategy. Here, we fabricated a multi-functionalized nanocarrier with a combination of chemotherapeutic agent and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy and improve entire anti-cancer index. Particularly, Paclitaxel nanocrystals (PTX NC) were first fabricated as a platform, on surface of which AuNPs were decorated and polydopamine (PDA) layer act as capping, stabilizing and hydrophilic agents for PTX NC, providing a bridge connecting AuNPs to PTX. These AuNPs decorated PTX NC exhibited good physico-chemical properties like optimal sizes, stability and photothermal efficiency. Compared to other PTX formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity and P-glycoprotein (Pgp) inhibitory capability, owing to a synergistic/ cooperative effect from AuNPs, PTX and NIR treatment, photothermal-triggered drug release and nano-scaled structure. Mitochondria-mediated signaling pathway is underlying mechanism for cytotoxic and apoptotic effect from AuNPs decorated PTX NC, in terms of Mitochondria damage, a loss of Mitochondrial membrane potential, intensified oxidative stress, DNA breakage, Caspase 3 activation, up-regulated expression in pro-apoptotic genes like p53, Caspase 3 and Bax and down-regulated level in anti-apoptotic gene like Bcl-2.

Gold Nanoparticle-Decorated Drug Nanocrystals for Enhancing Anticancer Efficacy and Reversing Drug Resistance Through Chemo-/Photothermal Therapy.

Limited chemotherapeutic efficiency, drug resistance, and side effects are primary obstacles for cancer treatment. The development of co-delivery systems with synergistic treatment modes should be a promising strategy. Here, we fabricated a multifunctionalized nanocarrier with a combination of chemotherapeutic agents and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy, thus enhancing overall anticancer efficacy, sensitizing drug-resistant cancer cells, and diminishing cancer stem cells (CSCs). To be specific, camptothecin nanocrystals (CPT NCs) were prepared as a platform, on the surface of which AuNPs were decorated and a hyaluronic acid layer acted as capping, stabilizing, targeting, and hydrophilic agents for CPT NCs, and reducing agents for AuNPs, providing a bridge connecting AuNPs to CPT. These AuNP-decorated CPT NCs exhibited good physico-chemical properties such as optimal sizes, payload, stability, and photothermal efficiency. Compared to other CPT formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity, Pgp inhibitory capability, and anti-CSC activity, owing to a synergistic/cooperative effect from AuNPs, CPT, near-infrared treatment, pH/photothermal-triggered drug release, and nanoscaled structure. A mitochondrial-mediated signaling pathway is the underlying mechanism for cytotoxic and apoptotic effects from AuNP-decorated CPT NCs, in terms of mitochondrial dysfunction, intensified oxidative stress, DNA fragmentation, caspase 3 activation, upregulation of proapoptotic genes such as p53, Bax, and caspase 3, and lower levels of antiapoptotic Bcl-2.

Aspartate Metabolism Facilitates IL-1ß Production in Inflammatory Macrophages.

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1ß (IL-1ß) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.

Hyaluronic Acid-Coated Camptothecin Nanocrystals for Targeted Drug Delivery to Enhance Anticancer Efficacy.

Tumor-targeted drug delivery via chemotherapy is very effective on cancer treatment. For potential anticancer agent such as Camptothecin (CPT), high chemotherapeutic efficacy and accurate tumor targeting are equally crucial. Inspired by special CD44 binding capability from hyaluronic acid (HA), in this study, novel HA-coated CPT nanocrystals were successfully prepared by an antisolvent precipitation method for tumor-targeted delivery of hydrophobic drug CPT. These HA-coated CPT nanocrystals demonstrated high drug loading efficiency, improved aqueous dispersion, prolonged circulation, and enhanced stability resulting from their nanoscaled sizes and hydrophilic HA layer. Moreover, as compared to crude CPT and naked CPT nanocrystals, HA-coated CPT nanocrystals displayed dramatically enhanced in vitro anticancer activity, apoptosis-inducing potency against CD44 overexpressed cancer cells, and lower toxic effect toward normal cells due to pH-responsive drug release behavior and specific HA-CD44 mediated endocytosis. Additionally, HA-coated CPT nanocrystals performed fairly better antimigration activity and biocompatibility. The possible molecular mechanism regarding this novel drug formulation might be linked to intrinsic mitochondria-mediated apoptosis by an increase of Bax to Bcl-2 ratio and upregulation of P53. Consequently, HA-coated CPT nanocrystals are expected to be an effective nanoplatform in drug delivery for cancer therapy.

Xanthophyllomyces dendrorhous-Derived Astaxanthin Regulates Lipid Metabolism and Gut Microbiota in Obese Mice Induced by A High-Fat Diet.

Astaxanthin is an important antioxidant with many biological activities such as anti-tumor, anti-obesity, cardioprotective, and immuno-modulatory activities. Most of these biological activities are derived from (3S,3'S)-astaxanthin, while the activities of (3R,3'R)-astaxanthin are rarely reported. The purpose of this study was to investigate the effect of (3R,3'R)-astaxanthin on lipid metabolism and gut microbiota in mice fed with a high-fat diet. In this work, 40 male C57BL/6 mice were divided into 8 groups fed a high-fat diet supplemented or not with (3R,3'R)-astaxanthin or Xanthophyllomyces dendrorhous for 8 weeks. The weight gain, energy intake, fat index, plasma triacylglycerol and cholesterol, liver triacylglycerol and cholesterol, and gut microbiota were determined. The results showed that the addition of (3R,3'R)-astaxanthin/X. dendrorhous to the high-fat diet as a supplement prevented weight gain, reduced plasma and liver triacylglycerol, and decreased plasma and liver total cholesterol. The addition of (3R,3'R)-astaxanthin/X. dendrorhous also regulated the gut microbiota of the mice, which optimized the ratio of Bacteroides to Firmicutes and increased the content of Verrucomicrobia, especially Akkermansia. The changes in the gut microflora achieved a healthier structure, thus reducing the incidence of obesity. Thus (3R,3'R)-Astaxanthin has the function of regulating lipid metabolism and gut microbiota to prevent obesity caused by a high-fat diet. The production strain of (3R,3'R)-astaxanthin, X. dendrorhous, has the same function as astaxanthin in preventing obesity caused by a high-fat diet, which reflects its potential ability as a probiotic drug.

Utilization of potato starch processing wastes to produce animal feed with high lysine content.

This work aims to utilize wastes from the potato starch industry to produce single-cell protein (SCP) with high lysine content as animal feed. In this work, S-(2-aminoethyl)-L-cysteine hydrochloride-resistant Bacillus pumilus E1 was used to produce SCP with high lysine content, whereas Aspergillus niger was used to degrade cellulose biomass and Candida utilis was used to improve the smell and palatability of the feed. An orthogonal design was used to optimize the process of fermentation for maximal lysine content. The optimum fermentation conditions were as follows: temperature of 40°C, substrate concentration of 3%, and natural pH of about 7.0. For unsterilized potato starch wastes, the microbial communities in the fermentation process were determined by terminal restriction fragment length polymorphism analysis of bacterial 16S rRNA genes. Results showed that the dominant population was Bacillus sp. The protein quality as well as the amino acid profile of the final product was found to be significantly higher compared with the untreated waste product at day 0. Additionally, acute toxicity test showed that the SCP product was non-toxic, indicating that it can be used for commercial processing.

Towards industrially feasible treatment of potato starch processing waste by mixed cultures.

The present study aimed at reducing the pollution of the waste generated by the potato starch industry to the environment and transform the potato pulp and wastewater into single-cell protein (SCP) to be used as animal feed. The chemical oxygen demand of the wastewater was reduced from 26,700 to 9,100 mg/L by batch fermentation with mixed cultures in an aerated 10-L fermenter. The SCP products, with a crude protein content of 46.09 % (higher than soybean meal), were found palatable and safe for mice. During the treatment process, the microbial community was analyzed using the terminal restriction fragment length polymorphism for bacterial 16S rRNA genes. The results of the analysis suggested that Curacaobacter/Pseudoalteromonas and Paenibacillus/Bacillus were the main microorganisms in treating potato starch processing wastes. The 150-m(3)-scale fermentation demonstrated a potential for treatment in industrial applications. Fermentation of potato pulp and wastewater without adding an extra nitrogen source was a novel approach in treating the potato starch processing waste.