Nanocrystalline Cellulose Modulates Dysregulated Intestinal Barriers in Ulcerative Colitis.

Ulcerative colitis (UC) is a recurrent chronic inflammation of the colon with increasing incidence and prevalence, which could increase the risk of colorectal cancer. It is urgent to find an effective method with few side effects. Nanocrystalline cellulose (NCC), which is from plant fibers, has a good biocompatibility and high biosafety. Herein, we used NCC to treat UC and evaluated its treatment effect by the disease activity index, intestinal pathology, inflammatory cytokines, tight junction proteins, and mucins. We studied the impact of NCC on mucin expression and gut microbiota to discuss the therapeutic mechanism. NCC can effectively treat UC by regulating the MAPK pathway of mucin 2 and the relative abundance of Akkermansia and Odoribacter, which could not cause the body damage. NCC could not cause body damage compared to the medications, while it had a better effect on the regulation of MUC2 compared to the present drug substitutes. NCC is a practical alternative for the treatment of UC.

The Antimicrobial, Hemostatic, and Anti-Adhesion Effects of a Peptide Hydrogel Constructed by the All-d-Enantiomer of Antimicrobial Peptide Jelleine-1.

Peptide hydrogels are believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and 3D printability. Most of the previously reported polypeptide hydrogels are composed of l-peptides, while the hydrogels formed by self-assembly of d-peptides are rarely reported. Herein, a peptide hydrogel constructed by D-J-1, which is the all-d-enantiomer of antimicrobial peptide Jelleine-1 (J-1) is reported. Field emission scanning electron microscope (FE-SEM) and rheologic study are performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies are carried out to evaluate its biofunction. The results show that D-J-1 hydrogel is formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π-π stacking force of aromatic ring in the structure of D-J-1. It exhibits promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibits good biocompatibility. Notably, D-J-1 hydrogel shows improved in vitro and in vivo stability when compared with its l-enantiomer J-1 hydrogel. Therefore, the present study will provide new insight into the application of d-peptide hydrogel, and provides a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use.

Ligand-Modified Gold Nanoparticles as Mitochondrial Modulators: Regulation of Intestinal Barrier and Therapy for Constipation.

Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.

Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.

The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers (CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.

Nanocrystalline Cellulose Cures Constipation via Gut Microbiota Metabolism.

Constipation can seriously affect the quality of life and increase the risk of colorectal cancer. The present strategies for constipation therapy have adverse effects, such as causing irreversible intestinal damage and affecting the absorption of nutrients. Nanocrystalline cellulose (NCC), which is from natural plants, has good biocompatibility and high safety. Herein, we used NCC to treat constipation assessed by the black stool, intestinal tissue sections, and serum biomarkers. We studied the effect of NCC on gut microbiota and discussed the correlation of gut microbiota and metabolites. We evaluated the long-term biosafety of NCC. NCC could effectively treat constipation through gut microbiota metabolism, which required a small dosage and did not affect the organs and intestines. NCC could be used as an alternative to medications and dietary fiber for constipation therapy.

A review on nanocellulose as a lightweight filler of polyolefin composites.

Nanocellulose (NC) possesses low density, high aspect ratio, impressive mechanical properties, nanoscale dimensions, which shows huge potential applications as a reinforced filler. Polyolefin (PO), represented by polyethylene (PE) and polypropylene (PP), has been widely used in industries. Recently nanocellulose/polyolefin nanocomposites (NC/PO nanocomposites) have caught more attention from the application of automotive components, aerospace, furniture, building, home appliances, and sport. In this review, the surface modifications of nanocellulose and polyolefin are summarized respectively, such as surface adsorption modification, small molecule modification, and graft copolymerization modification. The common preparations of NC/PO nanocomposites are discussed, including the melting compounding, the solvent casting, and the in-situ polymerization. The lightweight, mechanical properties, and aging-resistant properties of NC/PO nanocomposites are highlighted. Finally, the potentials and challenges for industrial production development of NC/PO nanocomposites are discussed.

Iron oxide nanoparticles for targeted imaging of liver tumors with ultralow hepatotoxicity.

Even though iron oxide (Fe3O4) nanoparticles are promising materials for magnetic resonance imaging (MRI) contrast agents, their biocompatibility and targeting efficacy still need to be improved. Herein, we modified glycyrrhetinic acid (GA) groups on Fe3O4 nanoparticles (Fe3O4@cGlu-GA) for liver tumor-targeted imaging. To evaluate the biocompatibility of these nanoparticles, we studied their cytotoxicity, hemolysis, and hepatotoxicity. We measured the uptake of Fe3O4@cGlu-GA nanoparticles in normal and liver tumor cells, then we investigated the specificity of Fe3O4@cGlu-GA nanoparticles in mouse models bearing subcutaneous and orthotopic liver tumors. With good biocompatibility and targeting efficacy both in vitro and in vivo, the Fe3O4@cGlu-GA nanoparticles are promising MRI contrast agents with ultralow hepatotoxicity and show great improvement on existing Fe3O4-based nanoparticles.

Fe3O4 nanoparticles modified by CD-containing star polymer for MRI and drug delivery.

Fe3O4 nanoparticles with ultrasmall sizes show good T1 or T1+T2 contrast abilities, and have attracted considerable interest in the field of magnetic resonance imaging (MRI) contrast agents. For effective biomedical applications, the colloidal stability and biocompatibility of the Fe3O4 nanoparticles need to be improved without reducing MRI relaxivity. In this paper, star polymers were used as coating materials to modify Fe3O4 nanoparticles in view of their dense molecular architecture with moderate flexibility. The star polymer was composed of a ß-cyclodextrin (ß-CD) core and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) arms. Meanwhile, reduced glutathione (GSH), as a model drug, was also associated with the star polymer. Thus, a new platform for simultaneous diagnosis and treatment was achieved. Compared to the Fe3O4 nanoparticles coated with linear polymers, the Fe3O4 nanoparticles coated with star polymers (Fe3O4@GCP) possessed higher GSH association capacity and better stability in serum-containing solution. GSH could be released from Fe3O4@GCP nanoparticles in response to pH value of the solution. Since the sulfhydryl group on GSH is able to combine free radicals, Fe3O4@GCP nanoparticles exhibited less cytotoxicity compared to the Fe3O4 nanoparticles without including GSH. Furthermore, the nanoparticles could also serve as good T1 MRI contrast agent, and the MRI relaxivity of Fe3O4@GCP nanoparticles did not decrease after coated with the star polymer. These results indicate that the precisely designed Fe3O4@GCP nanoparticles could be used as a versatile promising theranostic nano-platform.

A microfluidic indirect competitive immunoassay for multiple and sensitive detection of testosterone in serum and urine.

We demonstrate a microfluidic-based indirect competitive chemiluminescence enzyme immunoassay (MIC) for multiple, sensitive, reliable and rapid detection of testosterone in human serum and urine samples. As MIC can detect biomarkers in a cost-effective and easy-to-operate manner, it may have great potential for clinical diagnosis and point-of-care testing (POCT).

Using carboxylated nanocrystalline cellulose as an additive in cellulosic paper and poly (vinyl alcohol) fiber paper.

Specialty paper (e.g. cigarette paper and battery diaphragm paper) requires extremely high strength properties. The addition of strength agents plays an important role in increasing strength properties of paper. Nanocrystalline cellulose (NCC), or cellulose whiskers, has the potential to enhance the strength properties of paper via improving inter-fibers bonding. This paper was to determine the potential of using carboxylated nanocrystalline cellulose (CNCC) to improve the strength properties of paper made of cellulosic fiber or poly (vinyl alcohol) (PVA) fiber. The results indicated that the addition of CNCC can effectively improve the strength properties. At a CNCC dosage of 0.7%, the tear index and tensile index of the cellulosic paper reached the maximum of 12.8 mN m2/g and 100.7 Nm/g, respectively. More importantly, when increasing the CNCC dosage from 0.1 to 1.0%, the tear index and tensile index of PVA fiber paper were increased by 67.29%, 22.55%, respectively.

Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier.

Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl L-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.

Glycyrrhetinic acid-modified chitosan/poly(ethylene glycol) nanoparticles for liver-targeted delivery.

A liver-targeted drug delivery carrier, composed of chitosan/poly(ethylene glycol)-glycyrrhetinic acid (CTS/PEG-GA) nanoparticles, was prepared by an ionic gelation process, in which glycyrrhetinic acid (GA) acted as the targeting ligand. The formation and characterization of these nanoparticles were confirmed by FT-IR, dynamic light scattering (DLS) and zeta potential measurements. The biodistribution of the nanoparticles was assessed by single-photon emission computed tomography (SPECT), and the cellular uptake was evaluated using human hepatic carcinoma cells (QGY-7703 cells). The anti-neoplastic effect of the doxorubicin.HCl-loaded nanoparticles (DOX-loaded nanoparticles) was also investigated in vitro and in vivo. The results showed that the CTS/PEG-GA nanoparticles were remarkably targeted to the liver, and keep at a high level during the experiment. The accumulation in the liver was 51.3% at 3 h after injection; this was nearly 2.6 times that obtained with the CTS/PEG nanoparticles. The DOX-loaded nanoparticles were greatly cytotoxic to QGY-7703 cells, and the IC(50) (50% inhibitory concentration) for the free doxorubicin.HCl (DOX.HCl) and the DOX-loaded CTS/PEG-GA nanoparticles were 47 and 79 ng/mL, respectively. Moreover, the DOX-loaded CTS/PEG-GA nanoparticles could effectively inhibit tumor growth in H22 cell-bearing mice.