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Postsurgical localized chemotherapy for breast cancer recurrence (BCR) still faces many problems which dampen researchers' enthusiasm and discounted prognosis. Simple strategies with controllable toxicities are expected to address these hurdles. Lentinan (LNT) has excellent biocompatibility and notable antitumor activity but rather low bioavailability after intravenous or oral administration. Here, a sponge-like LNT/chitosan composite (LNT/CS sponge) was prepared for efficient local delivery to prevent postoperative BCR. The obtained sponges exhibit uniform porosity and sustained release of LNT in vitro and in vivo. Furthermore, the sponges were implanted and showed significant reduction of postsurgical recurrence and suppression of long-term tumor regrowth with favorable biocompatibility in a subcutaneous postsurgical recurrence mouse model. Subsequent studies revealed that LNT can restrain the stemness of breast cancer cells, which may account for the long-term inhibition of tumor relapse. Therefore, LNT/CS sponge has a great potential as a promising alternative for postsurgical BCR., (Copyright © 2021. Published by Elsevier B.V.)

Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro. SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lentinan (LNT), a typical triple helix β-glucan extracted from Lentinus edodes , has been widely used as a functional food and an orally administered drug. However, its oral pharmacokinetics has been rarely reported. The aim of this work is to systematically study the pharmacokinetics and intestinal absorption mechanism of LNT after oral administration. Radioactive 99m-technetium ( 99m Tc) was introduced to label LNT to determine the plasma concentration, tissue distribution, and excretion of the β-glucan in rats after oral administration. The results confirmed the absorption of LNT, with the maximal plasma concentration reached at 1 h. 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF) was used to label LNT to explore the absorption mechanism of LNT, utilizing both a Ussing chamber and a monolayer of Caco-2 cells. These transport assays showed that LNT could penetrate through the intestine and epithelial monolayer, which was mediated by macropinocytosis and clathrin-mediated endocytosis. These findings provide a pharmacokinetic reference for LNT and help provide a greater understanding of the absorption of β-glucans in general.

Lentinan, a β-1,3-D-glucan, is clinically used as an immune enhancement drug for tumor therapy. Dectin-1 is a cell-surface immune receptor, which plays an important role in immunological defense against fungal pathogens and β-glucan-mediated immune modulation. Herein we attempted to study the advanced structure of lentinan and how lentinan interacts with dectin-1 for its immune enhancement effect. We firstly used MD simulation and rigid macromolecule docking, combining some spectral techniques, to uncover the complex 3D conformation of a typical polysaccharide - lentinan, and the detailed interaction mode of lentinan with dectin-1. We proved by computational simulation that lentinan can maintain its triple-helix through hydrogen network and disclosed some structural properties of lentinan. We also characterized the affinity of lentinan to dectin-1 by LSPR and binding free energy calculation, and we found out that hydrogen bonds and CH-π interaction are the major contributors for lentinan's binding to dectin-1. Besides, after bound with lentinan, dectin-1 might surprisingly go through a conformational change. In summary, our work provided insights into lentinan's advanced structure and β-glucan recognition by dectin-1., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lentinan (LNT), a typical triple helix β-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other β-glucans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this study is to establish a rapid and sensitive method for detecting lentinan (LNT) in biosamples and to evaluate the pharmacokinetics of LNT in mice and rats. A diethylenetriaminepentaacetic acid (DTPA) derivative of LNT (DTPA-LNT) was synthesized first to allow labelling with 99m-technetium (99mTc). After purification and identification, 99mTc-DTPA-LNT was intravenously administered to mice (2 mg kg-1) and rats at different doses (0.5, 2 and 8 mg kg-1). The results showed that the 99mTc-labelling method was suitable for the quantification of the LNT concentration in biological samples, with satisfactory linearity (r2 > 0.998), precision (<7%), accuracy (95.01-104.51%) and total recovery (∼90%). The blood concentration-time profiles of 99mTc-DTPA-LNT were consistent with the two-compartment model and showed a rapid distribution phase and a slow elimination, and no significant difference in the blood level of LNT was found among the tested doses (0.5, 2 and 8 mg kg-1). LNT was predominantly incorporated into the liver and spleen, and there was a small amount of aggregation in the bile, kidneys, lungs and stomach. Approximately 40% of the administered radioactivity was detected in urine and faeces within 24 h post-dosing. In addition, SPECT imaging of 99mTc-DTPA-LNT was performed to visually reveal the pharmacokinetic characteristics of LNT. These findings provide a reference for further study and for use of LNT and other β-glucans.

Despite the great progress in the treatment of hepatocellular carcinoma, combination chemotherapy is still the main choice of treatment for patients with unresectable metastatic or recurrent hepatocellular cancer. Lentinan, which has been used as an immunomodulator in the treatment of cancer, possesses anti-tumor activities. However, the mechanisms by which Lentinan inhibits hepatocellular carcinoma remain unknown. Our study showed that Lentinan has a significantly synergistic anti-tumor effect with oxaliplatin against HepG2 cells in vitro and in H22 tumor-bearing mice through the mitochondria pathway and for the inhibition of NF-κB, Stat3 and survivin signaling. Moreover, Lentinan moderated side effects induced by oxaliplatin. These findings suggested that Lentinan may be an ideal agent for the combination therapy of oxaliplatin against hepatocellular carcinoma., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to evaluate the direct antitumor activity of edible fungal polysaccharide Lentinan, rather than as a host defence potentiator, on human breast cancer and investigate its underlying mechanisms. The present results revealed that there were 45.46% and 59.16% of inhibitory rate after Lentinan treatment in MCF-7 cells and tumor-bearing athymic nude mice, respectively. Annexin V-FITC/PI, H&E staining and TUNEL assay showed that Lentinan induced cell apoptosis which accompanied with abundant activated caspase-7, increased cytosol cytochrome c and Bax/Bcl-2. Unexpectedly, we firstly demonstrated that Lentinan could stimulate cell autophagy according to the detection of autophagosomes and autophagic flux. Pretreatment with autophagy inhibitors decreased Lentinan-induced cells death. These findings provided new insight into the mechanisms of Lentinan-antitumor effect and contributed to its development in functional foods and cancer therapy. [ABSTRACT FROM AUTHOR]

JLNT, a purified polysaccharide with the structure of β-(1→3)-D-glucose main chains and β-(1→6)-D-glucose side chains and with an average molecular weight of 605.4 kDa, was extracted and isolated from the fruitbodies of Lentinus edodes, which has immunoregulatory activity and anti-tumour effects. In the present study, we found that JLNT possessed direct anti-tumour effects on MCF-7 and S180 cells and apoptosis -inducing activity in S180 tumour bearing mice. Therefore, we investigated the mechanisms of JLNT-induced apoptosis. Results showed that JLNT increased the expression of p53, enhanced the Bax/Bcl-2 ratios by up-regulating Bax and down-regulating Bcl-2, promoted the expression of Smac, leading to the activation of caspase-3 and finally the initiation of cell apoptosis in S180 tumour bearing mice. Taken together, these findings provide the experimental evidence that JLNT could induce apoptosis of S180 cells via mitochondria pathways. [ABSTRACT FROM AUTHOR]

It had been shown that lentinan (LNT) was mainly distributed in the liver after intravenous administration. The study aimed to investigate the integrated metabolic processes and mechanisms of LNT in the liver, as these have not been thoroughly explored. In current work, 5-([4,6-dichlorotriazin-2-yl] amino) fluorescein and cyanine 7 were used to label LNT for tracking its metabolic behavior and mechanisms. Near-infrared imaging demonstrated that LNT was captured mainly by the liver. Kupffer cell (KC) depletion reduced LNT liver localization and degradation in BALB/c mice. Moreover, experiments with Dectin-1 siRNA and Dectin-1/Syk signaling pathway inhibitors showed that LNT was mainly taken up by KCs via the Dectin-1/Syk pathway and promoted lysosomal maturation in KCs via this same pathway, which in turn promoted LNT degradation. These empirical findings offer novel insights into the metabolism of LNT in vivo and in vitro , which will facilitate the further application of LNT and other β-glucans. [Display omitted] • A novel capsule polysaccharide (CPS-605) is obtained from Lactobacillus plantarum LCC-605. • AM is successfully conjugated with CPS-605 to generate CPS-AM NPs. • CPS-AM NPs significantly reduce the working concentration of amikacin. • CPS-AM NPs exhibit excellent antibacterial activity against Gram-negative strains. • CPS-AM NPs show great biofilm inhibition and disruption abilities. [ABSTRACT FROM AUTHOR]