A quaternary ammonium-based nanosystem enables delivery of CRISPR/Cas9 for cancer therapy.

Genome editing mediated by CRISPR/Cas9 is an attractive weapon for cancer therapy. However, delivery of CRISPR/Cas9 components to achieve therapeutic efficiency is still challenging. Herein, a quaternary ammonium-functionalized poly(L-lysine) and a cholesterol-modified PEG (QNP) were self-assembled with a negatively charged CRISPR Cas9/sgRNA ribonucleoprotein (RNP) to form a ternary complex (QNP/RNP).

Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans.

Aging is a dynamic and progressive process mediated by reactive oxygen species (ROS), and the antioxidant enzyme superoxide dismutase (SOD) can effectively scavenge ROS to extend longevity. However, the instability and impermeability of native enzyme limit its in vivo biomedical application. Currently, exosome as protein carriers attracts considerable attention in the disease treatment owing to low immunogenicity and high stability.

Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half-Life, Reduced Toxicity, and Increased Tumor Targeting.

Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers have been recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged.

Oral Administration of Therapeutic Enzyme Capsule for the Management of Inflammatory Bowel Disease.

Background: Oral administration of proteins/peptides is challenging in clinical application due to their instability and susceptibility in the gastrointestinal tract.

Materials And Methods: The in situ polymerization on the surface of enzymes was used to encapsulate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) in polymeric shells, and the reactive oxygen species (ROS) scavenging ability was monitored based on DCFH-DA probe using flow cytometry and confocal laser scanning microscopy. The mRNA expression level of pro-inflammatory factors was assessed by real-time qPCR, using lipopolysaccharide-induced RAW264.

Drug-free neutrally charged polypeptide nanoparticles as anticancer agents.

Cationic synthetic anticancer polymers and peptides have attracted increasing attention for advancing cancer treatment without causing drug resistance development. To circumvent in vivo instability and toxicity caused by cationic charges of the anticancer polymers/peptides, we report, for the first time, a nanoparticulate delivery system self-assembled from a negatively charged pH-sensitive polypeptide poly(ethylene glycol)-b-poly(ʟ-lysine)-graft-cyclohexene-1,2-dicarboxylic anhydride and a cationic anticancer polypeptide guanidinium-functionalized poly(ʟ-lysine) (PLL-Gua) via electrostatic interaction. The formation of nanoparticles (Gua-NPs) neutralized the positive charges of PLL-Gua.

Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo.

Multidrug resistant infections are plaguing the healthcare sector over the past few decades with limited treatment options. To overcome this problem, the authors synthesize a series of novel guanidinium-functionalized polypeptides. Specifically, poly(l-lysine) (PLL) with different lengths is first synthesized by ring-opening polymerization of N -benzyloxycarbonyl-l-lysine-N-carboxyanhydride (Lys(Z)-NCA) followed by functionalization with a guanidinium-functional group to obtain guanidinium-functionalized PLL (PLL-Gua).

Constituents of Morus alba var. multicaulis leaf improve lipid metabolism by activating the AMPK signaling pathway in HepG2 cells.

One new compound, 3Z-1-O-β-D-glucopyranosyl-3-hexene-1,5-diol (1), together with 26 known isolates (2-27) were obtained from the leaf of Morus alba var. multicaulis. Among the known compounds, 7, 11, 12, 14, 15, 18, 19, 23, and 24 were firstly obtained from the Morus genus; 2-5, 8, 10, 13, and 20 were firstly isolated from M.

Potent Antiviral and Antimicrobial Polymers as Safe and Effective Disinfectants for the Prevention of Infections.

Disinfection using effective antimicrobials is essential in preventing the spread of infectious diseases. This COVID-19 pandemic has brought the need for effective disinfectants to greater attention due to the fast transmission of SARS-CoV-2. Current active ingredients in disinfectants are small molecules that microorganisms can develop resistance against after repeated long-term use and may penetrate the skin, causing harmful side-effects.

Anti-inflammatory Limonoids From .

The root barks of perennial herb () were reported to be rich in anti-inflammation activity constituents, limonoids. Then, the investigation of anti-inflammation therapeutic limonoids from this plant was developed in the present study. Through the combination of various chromatographies isolation, six new limonoids, named dictamlimonol A (), dictamlimonoside B (), and dictamlimonols C-F (-), along with seven known ones (-), were obtained.

Isoprenoids obtained from Cortex Dictamni and their nitric oxide inhibitory activities.

Nine new isoprenoids, named as dictamtrinor-guaianols A (1), B (2), C (3), D (4), and E (5), dictamnorsesquiterpenol A (6), dictamnorsesquiterpenosides B (7) and C (8), as well as dictamtriterpenol A (9), along with eight known compounds (10-17) were obtained from 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the extensive spectroscopic methods and ECD data analysis. Moreover, LC-MS analysis result suggested compounds 2 and 3 were natural products.

Combretastatin A4 Nanoparticles Combined with Hypoxia-Sensitive Imiquimod: A New Paradigm for the Modulation of Host Immunological Responses during Cancer Treatment.

Vascular disrupting agents (VDAs) have great potential in cancer treatment. However, in addition to their direct tumoral vascular collapse effect, VDAs activate host immunological responses, which can remarkably impair their anticancer efficacy. Here, a VDA nanomedicine, poly(l-glutamic acid)--methoxy poly(ethylene glycol)/combretastatin A4 (CA4-NPs), is found to induce the intratumor infiltration of immature plasmacytoid dendritic cells (pDCs), thereby curtailing anticancer immunity.

Glucose and pH Dual-Responsive Nanogels for Efficient Protein Delivery.

Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half-life within the body. To overcome these challenges, pH and glucose dual-responsive biodegradable nanogels comprised of dextran and poly(L-glutamic acid)-g-methoxy poly-(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA) are designed. The cross-linked network imparted drug-loading efficacy of α-amylase up to 55.

Reversible Stability of Emulsion and Polymer Latex Controlled by Oligochitosan and CO₂.

The addition of salt to a colloid solution ensures that emulsions can be easily separated into two phases and that polymer latexes can be coagulated. The switchable stability of emulsions and polymer latexes would improve the properties for their current applications. A switchable process of salt addition can be achieved using CO₂ and switchable water, and it is a novel, benign approach to achieving a switchable ionic strength in an aqueous solution.

Anti-inflammatory constituents from Cortex Dictamni.

Eight new compounds named as dictamalkosides A (1), B (2), C (3), dictamphenosides A (4), B (5), C (6), D (7) and E (8), as well as 23 known ones were obtained from the 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the spectroscopic evidences. Among the known compounds, 14, 17-23, 25-28, and 31 were isolated from Dictamnus genus for the first time; 16 and 24 were firstly isolated from this plant.

Selectively Potentiating Hypoxia Levels by Combretastatin A4 Nanomedicine: Toward Highly Enhanced Hypoxia-Activated Prodrug Tirapazamine Therapy for Metastatic Tumors.

Hypoxia-activated prodrugs (HAPs) have the potential to selectively kill hypoxic cells and convert tumor hypoxia from a problem to a selective treatment advantage. However, HAPs are unsuccessful in most clinical trials owing to inadequate hypoxia within the treated tumors, as implied by a further substudy of a phase II clinical trial. Here, a novel strategy for the combination of HAPs plus vascular disrupting agent (VDA) nanomedicine for efficacious solid tumor therapy is developed.

Dihydroartemisinin increases gemcitabine therapeutic efficacy in ovarian cancer by inducing reactive oxygen species.

Ovarian cancer is the major cause of death in women gynecological malignancy and gemcitabine (GEM) is commonly used in related chemotherapy. However, more than 90% GEM is catalyzed into an inactive metabolite 2'-deoxy-2',2'-difluorouridine by stromal and cellular cytidine deaminase (CDA). Dihydroartemisinin (DHA), which possesses an intramolecular endoperoxide bridge, could be activated by heme or ferrous iron to produce reactive oxygen species (ROS).

Eudesmane-Type Sesquiterpene Glycosides from Dictamnus dasycarpus Turcz.

Eudesmane-type sesquiterpenes have been reported to exhibit varieties of biological activities. During the process of investigating this kind of natural product from the root bark of Turcz., 13 eudesmane-type sesquiterpene glycosides including six new isolates, named as dictameudesmnosides A₁ (), A₂ (), B (), C (), D (), and E (), together with seven known ones (-), were obtained.

Co-administration of genistein with doxorubicin-loaded polypeptide nanoparticles weakens the metastasis of malignant prostate cancer by amplifying oxidative damage.

Prostate cancer is a typical malignant disease with a high incidence and a poor prognosis. Doxorubicin hydrochloride (DOX·HCl) is one of the most effective agents in the treatment of prostate cancer, but severe side effects and metastasis after its treatment impose restrictions on its application. Herein, a combination of genistein (GEN) and doxorubicin-loaded polypeptide nanoparticles (DOX-NPs) is constructed for the treatment of prostate cancer.

pH and redox dual-sensitive polysaccharide nanoparticles for the efficient delivery of doxorubicin.

A pH and redox dual-sensitive biodegradable polysaccharide, succinic acid-decorated dextran-g-phenylalanine ethyl ester-g-cysteine ethyl ester (Dex-SA-l-Phe-l-Cys), was synthesized to load doxorubicin hydrochloride (DOX·HCl). The DOX-loaded nanoparticles, which were prepared in aqueous solution and free of organic solvent, could spontaneously self-assemble into uniform sizes. When loading DOX·HCl, mercapto Dex-SA-l-Phe-l-Cys was oxidized into a crosslinked disulfide linkage to form pH and redox dual-sensitive nanoparticles (DOX-S-NPs).

Bioactive Constituents from the Whole Plants of Gentianella acuta (Michx.) Hulten.

As a Mongolian native medicine and Ewenki folk medicinal plant, has been widely used for the treatment of diarrhea, hepatitis, arrhythmia, and coronary heart disease. In the course of investigating efficacy compounds to treat diarrhea using a mouse isolated intestine tissue model, we found 70% EtOH extract of whole plants had an inhibitory effect on intestine contraction tension. Here, nineteen constituents, including five new compounds, named as gentiiridosides A (), B (), gentilignanoside A (), (1)-2,2,3-trimethyl-4-hydroxymethylcyclopent-3-ene-1-methyl--β-d-glucopyranoside (), and (3)-3-hexene-1,5-diol 1--α-l-arabinopyranosyl(1→6)-β-d-glucopyranoside () were obtained from it.

Bioactive Constituents Obtained from the Seeds of Lepidium apetalum Willd.

Three new compounds, apetalumosides C₁ (), D (), and 1-thio--d-glucopyranosyl(1→1)-1-thio-α-d-glucopyranoside (), together with twenty-two known ones (4-25) were obtained from the seeds of Willd. Among the known isolates, -, -, -, and were obtained from the genus for the first time; , , , and - were isolated from the species for the first time. Meanwhile, the NMR data of 16 was first reported here.

Inhibitory Effects of Constituents from the Aerial Parts of Rosmarinus officinalis L. on Triglyceride Accumulation.

Sixteen flavonoids (-) including two new ones, named officinoflavonosides A () and B () were obtained from the aerial parts of . Among the known ones, , , and were isolated from the rosmarinus genus for the first time. Their structures were elucidated by chemical and spectroscopic methods.