Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy.

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4+ and CD8+ T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Effects of pork sausage on intestinal microecology and metabolism in mice.

BACKGROUND: Processed meat, as an important part of the human diet, has been recognized as a carcinogen by the International Agency for Research on Cancer (IARC). Although numerous epidemiological reports supported the IARC's view, the relevant evidence of a direct association between processed meat and carcinogenicity has been insufficient and the mechanism has been unclear. This study aims to investigate the effects of pork sausage (as a representative example of processed meat) intake on gut microbial communities and metabolites of mice. Microbial communities and metabolites from all groups were analyzed using 16S rRNA gene sequencing and Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF/MS), respectively. RESULTS: The levels of Bacteroidetes, Bacteroides, Alloprevotella, Lactobacillus, Prevotella_9, Lachnospiraceae_NK4A136_group, Alistipes, Blautia, Proteobacteria, Firmicutes, Allobaculum, Helicobacter, Desulfovibrio, Clostridium_sensu_stricto_1, Ruminococcaceae_UCG-014, Lachnospiraceae_UCG-006 and Streptococcus (P < 0.05) were obviously altered in the mice fed a pork sausage diet. Twenty-seven metabolites from intestinal content samples and fourteen matabolites from whole blood samples were identified as potential biomarkers from multivariate analysis, including Phosphatidic acid (PA), Sphingomyelin (SM), Lysophosphatidylcholine (LysoPC), Diglyceride (DG), D-maltose, N-acylamides and so forth. The significant changes in these biomarkers demonstrate metabonomic variations in pork sausage treated rats, especially carbohydrate metabolism, lipid metabolism, and amino acid metabolism. CONCLUSION: The present study provided evidence that a processed meat diet can increase the risk of colorectal cancer and other diseases significantly by altering the microbial community structure and disrupting the body's metabolic pathways. © 2023 Society of Chemical Industry.

Mg/Al-LDH as a nano-adjuvant for pertussis vaccine: a evaluation compared with aluminum hydroxide adjuvant.

Background. Layered double hydroxide (LDH) has been demonstrated as a highly efficient antigen platform to induce effective and durable immune response. However, whether LDH nanoparticles could act as an adjuvant for pertussis vaccines is still unknown. Here we evaluated the potential of Mg/Al-LDH as a nano-adjuvant to improve immune response against pertussis and compared it with commercial aluminum hydroxide (AH) adjuvant.Method. The Mg/Al-LDH nanoparticles were synthesized by a hydrothermal reaction. The morphology, structure and size of Mg/Al-LDH were characterized by transmission electron microscope, x-ray diffraction and MALVERN particle analysis. The ovalbumin and Pertussis toxin (PTd) was adsorbed to Mg/Al-LDH. The immune response of antigen-LDH complex was evaluated in mice, compared with commercial adjuvant alum. Hematoxylin-eosin staining was used to evaluate the inflammatory response at injection site.Results. The synthetic Mg/Al-LDH nanoparticles showed a typical hexagonal lamellar structure. The average size of synthetic nanoparticles was 102.9 nm with PDI of 0.13 and zeta potential was 44.4 mV. Mg/Al-LDH nanoparticles effectively adsorbed protein antigen and mediated antigen uptake by DC cells. Animal experiments showed that Mg/Al-LDH gave enhancement in anti-pertussis toxin (PTd) humoral immune response, which was considerable to commercial AH adjuvant. Finally, Mg/Al-LDH produced a slighter inflammatory response than AH at injection site and this injury was quickly recovered.Conclusion. Our study demonstrated the potential of Mg/Al-LDH as an effective adjuvant for pertussis vaccine, which induced comparable antibody response and had a better safety compared with commercial AH adjuvant.