RESUMEN
While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8+ T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
Asunto(s)
Biomarcadores de Tumor , Fenómenos Inmunogenéticos , Terapia Molecular Dirigida , Nanopartículas , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/terapia , Nanomedicina Teranóstica , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores/metabolismo , Fosfatos de Calcio/química , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Terapia Genética , Humanos , Inmunoterapia , Lípidos/química , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Nanopartículas/química , Nanopartículas/ultraestructura , Nanotecnología , Neoplasias/patología , Plásmidos/administración & dosificación , Plásmidos/química , Plásmidos/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , Transducción de SeñalRESUMEN
BACKGROUND: The present research was conducted to investigate the influences of supplementation with different levels of folic acids in diet on the performance of lactating sows. Twenty Landrace × Yorkshire sows received the same basal corn-soybean diets (folic acid, 1.3 mg kg(-1)) from gestation to parturition (day 107). After parturition, sows were allotted to four treatments: control group (folic acid supplementation level, 0 mg kg(-1)), group 1 (12.5 mg kg(-1)), group 2 (50 mg kg(-1)) and group 3 (100 mg kg(-1)), with five replicates of one sow. The experiment lasted for 21 days. RESULTS: (1) Folic acid increased milk production (P > 0.05). (2) Compared with the control, supplementation with folic acid (100 mg kg(-1)) increased the concentration of butter fat, total substance and non-lipoid substance significantly (P < 0.01), the concentration of milk protein was also significantly increased in group 2 and group 3 (P < 0.01) in milk. (3) Folic acid supplementation could increase litter weaning weight, average piglet weaning weight and average piglet daily gain (P > 0.05). CONCLUSION: These results suggested that supplementation with folic acid in the diets of lactating sows increases milk production, improved milk quality and the performance of piglets.
Asunto(s)
Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Lactancia/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Sus scrofa/crecimiento & desarrollo , Amoníaco/sangre , Animales , Animales Lactantes , Peso al Nacer , Nitrógeno de la Urea Sanguínea , Cruzamientos Genéticos , Femenino , Ácido Fólico/efectos adversos , Ácido Fólico/metabolismo , Lactancia/sangre , Metabolismo de los Lípidos , Tamaño de la Camada , Masculino , Leche/metabolismo , Proteínas de la Leche/metabolismo , Embarazo , Sus scrofa/fisiología , Destete , Aumento de PesoRESUMEN
The study was to determine effects of dietary supplementation of chitosan (COS) and galacto-mannan-oligosaccharides (GMOS) on some serum biochemical indices, serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and hepatic and long gissimus muscle IGF-I mRNA expression in early-weaned piglets. Twenty six Duroc x Landrace x Yorkshire piglets at the age of 15 days were used. The piglets had access to creep feed during the suckling. Six piglets were sacrificed for sampling at the beginning of the study. The other 20 piglets were individually housed in metabolic cages and randomly allotted to four corn and soybean meal-based diets including the control group, the antibiotic group with 110 mg lincomycin/kg diet, the COS group containing 0.025% COS, and the GMOS group with 0.20% GMOS, respectively, in a 2-week feeding experiment. Blood urea nitrogen (BUN) level was reduced whereas serum total protein concentration was increased (P<0.05) in responses to the COS and GMOS supplementation. Dietary supplementation of COS and GMOS also increased (P<0.05) the serum GH and IGF-I levels along with enhanced hepatic and the muscle IGF-I mRNA abundance. Dietary supplementation of oligosaccharides such as COS and GMOS may improve growth and feed conversion efficiency by increasing plasma GH and IGF-I levels, in the early-weaned piglets.