peu-MIR2916-p3-enriched garlic exosomes ameliorate murine colitis by reshaping gut microbiota, especially by boosting the anti-colitic Bacteroides thetaiotaomicron.

Plant-derived exosome-like nanoparticles (ELNs) have drawn considerable attention for oral treatment of colonic diseases. However, the roles of ELNs derived from garlic on colitis remain unclear. Here, we demonstrate that garlic ELNs (GELNs), with desirable particle sizes (79.60 nm) and trafficking large amounts of functional proteins and microRNAs, stably roam in the gut and confer protection against ulcerative colitis (UC). In mice with DSS-induced colitis, orally administered GELNs effectively ameliorated bloody diarrhea, normalized the production of proinflammatory cytokines, and prevented colonic barrier impairment. Mechanistically, GELNs were taken up by gut microbes and reshaped DSS-induced gut microbiota dysbiosis, in which Bacteroides was the dominant respondent genus upon GELNs treatment. Notably, GELNs-enriched peu-MIR2916-p3 specifically promoted the growth of Bacteroides thetaiotaomicron, an intestinal symbiotic bacterium with palliative effects on colitis. Our findings provide new insights into the medicinal application of GELNs and highlight their potential as natural nanotherapeutic agents for preventing and treating UC.

Human neutrophil membrane-derived nanovesicles as a drug delivery platform for improved therapy of infectious diseases.

Resolvins are a group of specialized proresolving lipid mediators (SPMs) enzymatically produced from omega-3 fatty acids during acute inflammation response to infections or tissue injury. Resolvin D1 (RvD1) is one of resolvins and is well studied in resolution of inflammation to treat inflammatory diseases. Resolution of inflammation includes the inhibition of polymorphonuclear leukocyte recruitment and reduced cytokine production. However, effective delivery of RvD1 to inflammatory tissues is challenging because of its lack of tissue targeting and poor physicochemical properties. Here, we proposed nanovesicles made from human neutrophil membrane which can specifically target inflamed tissues, and we loaded RvD1 on the surface of nanovesicles and antibiotic (ceftazidime, CEF) inside nanovesicles for improved treatment of bacterial infections. In a mouse model of bacterium-induced peritonitis, we demonstrated that human neutrophil cell membrane-formed vesicles (NMVs) enhanced inflammation resolution and bacterial killing after co-delivery of RvD1 and CEF. Our studies reveal that neutrophil nanovesicles may be critical for enhanced therapy to infectious diseases.

Co-delivery of docetaxel and silibinin using pH-sensitive micelles improves therapy of metastatic breast cancer.

Breast cancer is the most vicious killer for women, and tumor metastasis is one of the leading causes of breast cancer therapy failure. In this study, a new pH-sensitive polymer (polyethylene glycol-block-poly[(1,4-butanediol)-diacrylate-ß-N,N-diisopropylethylenediamine], BDP) was synthesized. Based on BDP, docetaxel/silibinin co-delivery micelles (DSMs) was constructed. DSM had a well-defined spherical shape under the transmission electron microscope with average hydrodynamic diameter of 85.3±0.4 nm, and were stable in the bloodstream but could dissociate to release the chemotherapeutic agents in the low pH environment of the endo/lysosomes in the tumor cells. Compared with free drugs, DSM displayed greatly enhanced cellular uptake, higher cytotoxicity and a stronger anti-metastasis effect against mouse breast cancer cell line 4T1. In 4T1 tumor-bearing mice treated with DSM (twice a week for 3 weeks), the inhibition rate on tumor growth and metastasis reached 71.9% and 80.1%, respectively. These results reveal that DSM might be a promising drug delivery system for metastatic breast cancer therapy.